A sequel was once in the works for the game, though very few screenshots and only one gameplay video were ever released. These materials revealed new playable characters such as The Hulk and The Juggernaut. However, due to poor game sales and the eventual closing of EA and Marvel's partnership in 2008, the game was eventually cancelled.

The game was first announced as "Marvel vs. EA", in reference to how it featured several iconic Marvel characters going up against a group of original characters created by Electronic Arts. In March 2005, the game's final title was revealed, as well as the involvement of comic artist Jae Lee and designer Paul Catling in the creation of EA's original characters, the titular Imperfects. This game and the 2005 promotional tie-in comic "Marvel Nemesis: The Imperfects" are their only major appearances in any Marvel property to date, likely because of the game's poor reception. While it was previously thought that EA owned the rights to the Imperfects since they created them, comic book writer Jonathan Maberry revealed in 2012 that Marvel actually owns the rights to them.