Cain was the first son of President Richard Withers, and was a senior member of the US military during the Civil War. In these early days, Cain lead the Incarnates program with his childhood friend Captain Hank Henriette and genuis bioengineer Dr. Elaine Bluelake, with Bluelake being in charge of converting volunteer human soldiers into "Incarnates" (monstrous creatures with God-like powers and strength) in order to ensure their victory in the war. Because of his father's refusal to allow any son of his to become an incarnate, Hank renounced his family name and replaced it with "Madhouse".
After many successful missions, Cain came into Hank's tent to congratulate him and his Incarnate squadron on their victories. In fact, Cain had been ordered to wipe out all incarnates, as a peace treaty was underway and the incarnates would be unable to adjust to the modern world and likely become a threat to mankind. For this purpose, he ordered Elaine (who had already converted Cain into an incarnate of human appearance) to create several so-called godkiller bullets.
In Hank's tent, he informed him that Elaine had wanted to see him to "tell him something" (in fact, he had ordered Elaine to kill Hank simply to toy with her, as he knew that she was in love with him).
Outside the barracks, Elaine repeatedly apologised to Hank about having to kill him, but knew that it was the only way to protect humanity from the incarnates, so she shot him in the stomach and apparently killed him, just as Cain had ordered. She then handed the godkiller bullets to Cain, and told him that she would go on executing other incarnate members as he had instructed before she and Cain would kill themselves, destroying any possibility of the Incarnates being recreated. Hank initially thought that Cain was doing all this for Elaine, to prevent her from having a legacy of death and regret. These thoughts were proven false immediately when Cain turned his gun on Elaine, said "You two are the only ones who will die!", and shot her dead, before laughing hysterically.
Having successfully unleashed the Incarnates upon the world, Cain went underground for a time, using his powers to manipulate and cause pain among others for his own amusement, while amassing an Incarnate army of his own and keeping it at his mansion. He resurfaced in the town of Whitechurch ten years later, when he and his young maidservant came to investigate sightings of his former underling Christopher Keynes, an incarnate who had come to resemble a gargoyle and become a serial killer operating out of the Whitechurch area.
Upon entering the town, his maidservant and he were propositioned by two prostitutes, and Cain initially accepted their advances, before staring into the eyes of one of the girls and using his powers to brainwash her mind into that of a ravenous beast driven solely by hunger. The brainwashed girl then attacked her friend and chewed her throat out, while Cain smiled, before becoming bored by the sight and walking off with his maidservant, declaring that a world with "dull evenings" like this make the world's existence utterly pointless.
Becoming the second serial killer in the town of Whitechurch, Cain set about finding the first and using him to draw out Hank (whom he had discovered survived Elaine's attack).
Cain then met up with "Gargoyle" (Christopher Keynes) in the abandoned White Church, for which the town was named. He then supplied Gargoyle with one godkiller bullet for the sole purpose of killing Hank. After Gargoyle failed to kill Hank and was killed with a fatal headshot by Hank's travelling companion Nancy Schaal Bancroft (who was generally referred to by her middle name only), Cain and his maidservant suddenly appeared in the church to Hank and began toying with his emotions for amusement, causing Hank to shoot him in the head.
After being shot, black flames started emanating from Cain's bullethole, as his face healed itself completely. His underling Elizabeth Weezer, aka Arachne, (a giant human-spider hybrid-type incarnate) then revealed herself to have been hiding behind Schaal and Hank, identified Cain as being a "very special type of Incarnate", calling him "The Undead King of Blood and Night, before Schaal and taking her as Cain's hostage. Cain then invited Hank (under the presumptive threat that he would kill Schaal if he refused) to a formal party which would occur later that week at his manor house. Cain then bid his former "friend" farewell, before jumping from the window alongside his maidservant, and making his getaway, while Arachne scuttled away with Schaal.
At Cain's mansion, Arachne forcibly undressed Schaal and put her in a somewhat revealing but still formal dress for the gala. At the gala, Hank and fellow Beast Hunter Liza arrived at the gala with hopes of rescuing Schaal from Cain and discovering his true plans. While at the gala, one of its many rich guests asked Hank if he was another of Cain's beneficiaries, but before he could answer Cain himself appeared on the ballroom's raised stage, and gave a speech thanking his beneficiaries and elaborating on the economic effects of the Civil War and how it had hampered all of their estates, before carefully changing the subject to make it seem that no peace treaty should have been written, and that the morally right thing to do would have been to use the Incarnates to finish the war by completely obliterating all who rebelled, calling his former military commanders "Cowards who were just scared of the incarnates' might".
Cain then said "And now, thanks to everyone's support, preparations are complete", before releasing fog into the ballroom, which lifted to reveal that the room was filled with incarnates. Cain the declared that, having been given their money for his campaign, his beneficiaries were no longer of any use to him, and ordered the incarnates to kill them all, whilst he smiled, taking immense pleasure out of their horrific deaths. Hank tried to plead with Cain to stop them, prompting Cain to remind him that Elaine had said that "All incarnates eventually lose their humanity", before lecturing Hank on the true meaning of humanity as a concept, all the while arguing hat he hadn't lost his, all in order to try to convince Hank to join him in his plan to reignite the Civil War and create a new era dominated by the stronger form of humanity: The Incarnates.
When Hank refused to follow any part of Cain's horrific plot, Cain revealed that Schaal's dress had in fact been made entirely out of Arachne's silk, and was still connected to Arachne's body. Arachne then dragged Schaal up onto the stage using the thread, while Cain promised to "steal away everything that binds you on this dreadfully dull evening", sensing that Hank had feelings for Schaal. As such while a horrified Hank ran towards the stage to try to save her, a smiling Cain pulled out a revolver from inside his coat and shot Schaal in the stomach, after which Arachne dropped her to die on the floor.
Losing control of his abilities at the sight of Schaal dying, Hank transformed into his white wolf-like incarnate form, all the while Cain egged him on to give into his "true nature", this time going further into his transformation than he ever had since the Civil War ended, becoming too big to be contained by Cain's mansion, destroying its roof. At the sight of what he'd done, Cain started laughing hysterically, before shouting to his army "Behold, you stand before Hank, Lord of the Beasts!"
One year later, it was revealed that Cain's bullet had failed to kill Schaal due to the protection Arachne's silk had given her. Cain meanwhile had significantly increased his influence and was seen delivering a speech to several hundred former southern troops and disruntled former civillains who now belonged to an army he commanded, which sought to take control of both North and South. Within only a few months, Cain had almost control of almost the entire "Patrian" continent, and was last seen entering a room holding a mysterious crystal, before looking into a chamber which contained Elaine, naked and being kept alive (but in a state of suspended animation) by a mysterious jelly-like substance, still with a large bulletwound in her right breast. Cain mocked her in her state by telling her that the new world she tried to kill would soon become a reality.
From his new temporary base at Bold Creek Fortress, Cain then began dispatching some of the more psychopathic incarnates such as Centaurus to gleefully wipe out entire northern army batallions. During one of these raids, he sent Centaurus to attack civilians near to his brother Claude's Incarnate Extermination Unit, where his pawn engaged in a violent and prolonged duel with Hank which led to his (Centaurus's) death. This attack however was nothing more than a diversion, so that Cain could attack Claude and Colonel Wall's camp directly. While Liza and Schaal hid from him, Cain waltzed straight into their camp and sadistically smiled as he tried out new powers he had developed through self-experimentation: the ability to make human bodies explode with the gesture of his hand. He slaughtered every soldier he encountered as he made his way to the battlefront where Claude and Wall were in combat. Using this power, he announced his presence to Wall by blowing the heads off of four of Wall's men, and expressing disgust at Wall's military tactics, before using his powers to blow out Wall's throat, killing him. Cain then confiscated a vial of anti-incarnate serum from Wall's corpse, and looked to his brother Claude with murderous intent. At this point, Hank threw a spear at Cain, which narrowly missed him, and told Claude to get out of the way, saying "He is mine!"
Nonetheless, Claude pointed his pistol at his brother, only to be mocked by Cain for his inability to shoot him, calling him nothing more than a puppet of their father with no will of his own and joking at how useless Claude's regular bullets are against him. Hank was able to convince Claude to leave his brother in order to avoid continuous psychological torture, and drew his spear to face Cain. Cain asked Hank whether the death of Centaurus had been a dignified end or one that was horifically cruel, but Hank ignored him and asked why Cain had only sent one incarnate to face him when he has hundreds at his disposal. This prompted Cain to reveal a demented smile as Hank realised that Cain had only sent Centaurus as a diversion so that he could attack the townspeople of Bold Creek and claim the region as his territory.
Cain then asked Hank how he had been since he had unleashed his true strength in Whitechurch and become the Lord of the Beasts., and asked whether or not he had discovered the joy of that power. In his fury, Hank continued to slash at Cain, being the only person skilled enough to match Cain's speed and dodge his supernatural attacks. When Hank commented that he was stronger than Cain, Cain grabbed Hank's hands and crushed them between his own fingers, telling him that their diffeerence in strength hadn't been true for years, and began to drink the blood from Hank's crushed hands, saying "Hank... you are delicious. The doomed overconfidence of thinking you know your enemy so well... impatience... confusion... and an inexhaustible hatred, sparked with rage and bloodlust... A truly complex, mellow sweetness. He then told Hank that it was about time he got going, that he hoped he survived to see the "Era of Gods", and vanished in a puff of smoke as Hank lunged at him with his bloody fist. Meanwhile, Claude and the remainder of his company fled to protect the town, only to discover that the young girl who had been accompanying Cain had used her powers to convert all of the town's residents into mindless, cannibalistic zombie-like monsters, whom Claude's men were forced to kill.
Having successfully orchestrated the massacre of an entire town of innocent people at the hands of the northern forces, Cain personally visited the presidential offices in Newfort to blackmail his father, threatening the crowd of innocent people outside the building with giant incarnates, whom he had ordered to kill the civilians should trouble arise. Cain jovially told his father how the townsfolk of Bold Creek had been massacred by Claude's men, and smiled sadistically when his father told him "This was all your doing."
Cain then asked his father what he would do next. He acknowledge that if he lost any of the giant incarnates he had taken into Newfort, his military forces would have no chance at victory, but also pointed out to his father that the government had only maintained control of a small number of cities including the capital. Therefore, Cain concluded, neither side could win. Enraged, President Withers furiously asked Cain what he wanted out of this war, suggesting options such as revolution and revenge against him. These suggestions sent Cain into a fit of laughter, and he said" Revenge? Ha ha ha. I want nothing. War holds little meaning for me. I'm simply giving the people and the incarnates what they want... Entertainment, Mr. President." With this, he paradoxically forced his father to sign a peace agreement that formally ended the fighting.
After returning to his base, Arachne and the young girl who frequently accompanies him, revealed to be named Migileglia, approached Cain and sat with him. When Arachne asked Cain why he didn't order Winters to give him more territory in the peace accord, or simply kill his father and take over the entire nation, Cain answered that doing either of those things would have had a boring outcome, and that showing no mercy is bad for PR. He said that it was enough for the incarnates to simply be happy with their lives, and told the two incarnate women that there was no need to be impatient, before turning his head to Migileglia and asking her to study the Word of God, before turning his head to look at Elaine in her tank.
Soon after this, Robin Arbell, an incarnate also known as Doppelganger, approached Cain desperate to be killed by him, knowing that Cain had Godkiller bullets. Robin had lost control of his power to create savage monsters out of his flesh, and had unintentionally illed so many people that it had driven him to suicidal despair. When he approached Cain, he begged Cain to kill him, but Cain had other plans for Robin. Cain knew Robin well from the war, and was excited at the prospect of unleashing an uncontrollable, murderous monster on a town on unsuspecting people, so he had Robin taken to a medium-sized town, where he (Robin) unintentionally multiplied into countless ravenous beasts that slaughtered all of the townspeople. Eventually, Robin was dealt a mercy-kill by Hank, and told him that his final wish was to prevent Cain from creating any more incarnates.
Cain is an intensely manipulative individual whose way with words often leads people to believe that he should be viewed as the victim of his circumstances and brings him many allies. His true nature is far darker, being extraordinarily sadistic even to those whom he claims to view as friends and has known for years, such as when he manipulated Elaine into shooting the man she loved before killing her out of spite. He has also shown that he is more than happy to turn on his own allies if they annoy him, or even if they simply lose their usefulness to him, irrespective of whether or not they fully support his goals, and his frequent smile while killing demonstrates the true depths of his sadism. He is also exceedingly arrogant, especially since becoming an incarnate, flaunting his inability to die by getting as close to his foes as possible and mocking the futility of their attempts to stop him.
Cain is also frequently bored, even quickly becoming bored by his own actions, and his boredom caused him to develop quite a nihilistic worldview, with him even saying at the end of vol.1 that "a world as boring as this does not have any point in existing". His nihilism is also demonstrated during his speech to Hank before his attempt to kill Schaal, where he says that nobody had any right to judge the humanity or morality of others, believing that morality is a pointless mental construct, and anything that started off as human and remains alive will never truly lose its humanity, because it is biologically human. His propensity for boredom is revealed in volume six to be his primary motivation for his cruel acts, since he cruelly reveals to his father (after having an entire town full of innocent people murdered) that everything he was doing was for the purpose of his own entertainment.
In the fourth volume, it is made abundantly clear by his brother Claude that before becoming an incarnate, Cain had been a far more kind and "gentle" individual, and Claude is unable to understand how his brother's mind became so utterly twisted and cruel. Nonetheless, Cain's father in the sixth volume seems to believe that Cain had always been utterly heartless, referring to him as The Devil when talking about him to his advisers.