Teenage Mutant Ninja Turtles: Mutant Melee is a 3D fighting game based on the 2003 animated series. The combat system is similar to the earlier games based on that series, but unlike them, it is a competitive vs. fighting game. It is not a traditional one-on-one fighter, but an arena-based, four-player game - somewhat along the lines of Power Stone.

There are two game modes. There is a single-player adventure mode in which you must guide one of ten characters (including six unlockables) through a series of 100 bouts that have you either beating up enemies, or, in a few cases, dodging bombs for a set amount of time. Completion of these portions unlocks the additional characters, bonus characters and stages for melee mode.

Melee mode is the multiplayer portion. It has ten basic and twelve unlockable characters, and nine basic and fifteen unlockable stages. There are four game types which mirror popular types from first-person shooters. There is a deathmatchesque knock-out mode, where the goal is to score the most KOs. (Players respawn after being KOed.) There is also a Last Man Standing mode, where the goal is to be the only player left when the others are KOed, a King of the Hill, where you must stand on a glowing patch of ground and defend it from other players, and a Keep away mode, where you must hold a treasure chest and avoid other players who are trying to beat you up and take it.