Misfire was part of a division led by Scourge and Cyclonus who attacked Autobot City to cause a distraction while Runabout and Runamuck stole the Key to the Plasma Energy Chamber. After Scourge successfully activated the chamber on Cybertron and inadvertently sent a shuttle full of Autobots along with the key halfway across the galaxy, Misfire was among the Decepticon unit sent to retrieve the key. Tracking the Autobots to Nebulos, Misfire and the Decepticons soon got into a skirmish with the Autobots
Maybe Misfire would aim better if he held his gun right. After being defeated and pushed back by the new Autobot Headmasters, the Decepticons made a deal with the Hive to donate their heads and weapons for the binary bonding process. Misfire thus became the Targetmaster partner of the Hive Nebulan Aimless.
Transformers: The Headmasters
Misfire and his fellow Targetmasters Slugslinger and Triggerhappy allied themselves with Scorponok to assist him in his siege of the planet Master. When a group of six refugees fled the planet seeking aid, the three Targetmasters and Sixshot went after them. The Decepticon Targetmasters soon encountered their old foes, the Autobot Targetmasters Pointblank, Sureshot and Crosshairs. However, the fighting was interrupted when the plasma energy bombs aboard the battleship preemptively exploded.
The Targetmasters later participated in the final battle at the North Pole against the Autobots, only to retreat into space after Scorponok was defeated and killed.