Arnim Zola's machine body was deactivated and put away at Shield's Triskelion archives where it was discovered by Spider-Man and Iron Spider. Once Zola reactivated, he noticed Amadeaus Cho as a fellow scientist and persuaded him to give him his ESP Box. Spider-Man warned Cho not to, but the ESP Box automatically attached itself to Zola, allowing him to reassemble his body. Arnim Zola then made his escape as he magnetized Iron Spider's armor, pinning him and Spider-Man against a wall and attractive several crates at them. Iron Spider and Spider-Man managed to track Arnim Zola at the Triskelion's underground laboratory and brought the help of Power Man and Agent Venom there. Once they encountered Zola, Zola summoned an army of synthetic creatures called Synthezoids and unleashed them upon the heroes. As the heroes struggle to fight the Synthezoids, Spider-Man tells Iron Spider to send a text message that Whizzer soon recieved and appeared to help. Once Whizzer arrived, he advises the heroes to target the ESP Box on Zola's head which Iron Spider acknowledged as he sent a signal, disrupting Zola's link to the Synthezoids, causing them to be unstable and the laboratory to collapse. As Whizzer manages to get everyone but Spider-Man out, he punches Arnim Zola in the face but is then knocked in an explosion. After Spider-Man get Whizzer to safety, he went back to the laboratory and found Zola trapped under rubble. Before Arnim Zola deactivated, he tells Spider-Man that a lot has changed in his absense, but believed the world is still worth conquering.
Arnim Zola later returned and captured Spider-Man who woke up in a tube that began to fill with a raw Synthezoid substance. Luckily Spider-Man freed himself and found himself in his dorm room. Spider-Man tried to show the other heroes the news, but they didn't believe him and thought he didn't get enough sleep. However, a moment later, a Synthezoid soon appeared and attacked Spider-Man. Spider-Man managed to defeat the Synthezoid and reported to Nick Fury. Nick Fury assumed Spider-Man was in a lab sleep study and showed him a tube that he suggested to go inside to help him wake up. Spider-Man agreed, but then realized Nick Fury would never call him his friend after he called him that. Suddenly, Nick Fury assaulted him as Spider-Man soon realized his eyepatch was on the wrong eye. Spider-Man then tasered Nick Fury to reveal him as a Synthezoid as he melted. As Spider-Man soon discovered it, Arnim Zola appeared and revealed he replaced Nick Fury and several Shield Agents with Synthezoids. Spider-Man soon encountered Synthezoid versions of Nova, Squirrel Girl, Power Man, Kazar and Zabu and got into a brief fight with them. As soon as he eluded them, he returned to his dorm room to show Iron Fist and Iron Spider the assimilation tube he was in. The heroes managed to track Arnim Zola's signal and made their way, but were then re-encountered by the Synthezoid heroes. Iron Fist managed to drench them with in water, allowing Spider-Man to taser them and melt them into goo. However, more Synthezoids appeared and captured Iron Fist and Iron Spider, leaving Spider-Man to retreat to the security center. There he found the remaining heroes: Agent Venom, White Tiger, Rhino, Cloak and Dagger. Together they head over to a laboratory where Arnim Zola's Synthezoids were being created. Arnim Zola soon appeared to tell Spider-Man that his efforts will have no effect. Rhino, on the other hand, tried to stop a machine from creating a Synthezoid version of Kazar, only to transform the clone into a hybrid of Zabu. The machine then created a hybrid of Nova and Power Man, then another of Iron Fist and Iron Spider. While fighting the Synthezoid hybrids, White Tiger revealed herself to be a Synthezoid. As the Synthezoids overwhelmed them, the heroes lured them to the training room to subdue them there. Even though Dagger was captured by some of the Synthezoids, Cloak managed to gather the rest of the Synthezoids in a pile that Spider-Man soon crushed them with a wall. The heroes then made their way outside to see the Tricarrier fly away after Cloak sensed Dagger was there along with the other captives of Arnim Zola. Arnim Zola soon appeared and launched several missiles at the Triskellion, demolishing it in the process.
Once Spider-Man and the remaining heroes arrive at the Helicarrier, Arnim Zola created villain hybrids that fought the heroes and succeeded in capturing Cloak.