Marvel: Ultimate Alliance 2 is the second game in the Marvel: Ultimate Alliance series, and is loosely based on the events of the Civil War comic book story line. It brings with it a larger roster of heroes and villains to play as, as well as more ways to utilize your team in battle.

The story opens as Nick Fury leads an unsanctioned team of heroes, including Captain America, Wolverine, Spider-Man, and Iron Man, in a covert strike on Castle Doom in Latveria, after discovering that its prime minister has been funneling weapons to supervillains. A year later the enemy returns seeking revenge, unleashing destruction on New York City. In the wake of the devastation and Fury's unlawful actions, the United States government begins weighing the Superhuman Registration Act. When a later catastrophe claims hundreds of civilian lives, the act is pushed through, fracturing the superhero community into bitter opposing camps. As Captain America and his allies go underground while Iron Man backs the new law, players are drawn into this civil war and must choose whether to stand with the pro-registration or anti-registration side.