Marvel Ultimate Alliance 2 follows the same basic gameplay patterns as its predecessor. The game allows to players to choose four heroes from a roster at any given time to play through the game.

Players will also have the ability to level up characters and earn new abilities and powers. Vicarious Visions have made changes in the game and camera controls for greater fluidity during gameplay.

The Comic-Con 2008 trailer shows an improvement in the power combo system; instead of merely doing some extra damage, two combined powers will yield a new attack altogether, such as Invisible Woman creating a force field and Iron Man overloading it with energy, effectively creating a bomb, or even the classic Fastball Special maneuver.