The sequel to 2003's updated beat 'em up, Teenage Mutant Ninja Turtles 2: Battle Nexus sets the turtle quartet on another adventure from the series' second season, this time allowing the entire team to work together via a 4-player multiplayer mode.

Each turtle now has their own unique ability and special fighting moves that fit in with their personality: such as operating switches and computers, or moving or destroying stationary objects. In single-player mode, players can switch turtles on the fly in order to accomplish the various tasks. Throughout some levels, the turtles also have racing sections over various terrains.

As players progress through the game, they can find secret items, abilities, and power-ups, including the original late 1980's Teenage Mutant Ninja Turtles arcade game.