Diamondback is one of the villains whose powers and armor were enhanced by the Tinkerer prior to the events of the game. Her first in-game appearance is working with the other villains helping Lucia von Bardas attack New York. After that attack is thwarted, Diamondback is locked up and eventually ends up in the Negative Zone prison, where she and other villains are infected with Mister Fantastic's control nanites. The main operating network of the nanites later becomes sentient and seizes control. Iron Man, Captain America, and Nick Fury's team fight her, Whirlwind, and Moonstone at the prison's exit portal to buy Fury time to set up the prison's self-destruct as a last-ditch effort to stop the nanite-controlled villains from escaping and infecting more people.