Prior to the game, Nick Fury and his superiors had discovered that the Tinkerer was responsible for augmenting the powers and armor of several supervillains. Some time later, Nick Fury found evidence proving that he was receiving support from Lucia von Bardas, acting ruler of Latveria at the time. But because of the work she put into mending relations between Latveria and America, Nick Fury was denied government support for his efforts to investigate the connection. Thus, Nick Fury talked several heroes into accompanying him on a mission into Latveria to shut down the Tinkerer's operation.
During the raid on Castle von Doom, several heroes encounter the Tinkerer in the labs and fight several of his creations, including a large tank-like structure he uses in an attempt to get rid of them. After the fight, the castle's reactor goes critical, causing the place to explode just as Nick Fury and the rest of his team escape.
Some time later, Nick Fury talks the Tinkerer into helping him investigate the source of the disturbance that cost the pro-registration forces their control over the nanite-infused supervillains. Upon receiving data sent from a computer in the Negative Zone prison, the Tinkerer discovers that the nanites used to control the villains became sentient and took control. The Tinkerer went off the radar after the heroes escaped the prison, which became overrun by nanite-controlled prisoners.
Some time later, it's revealed that the Tinkerer was recruited by the nanites, now calling themselves The Fold, for technical support. On their way to shut down the nanites, the heroes not infected by The Fold fight the Tinkerer, who is accompanied by several nanite-controlled soldiers. He escapes and blocks the stasis signal from the top of the tower, only to be knocked out by the heroes once they reach the top.