Teenage Mutant Ninja Turtles: Smash-Up is a fighting video game for the Wii and PlayStation 2 video game consoles. It was developed by Game Arts in cooperation with Mirage Studios and released by Ubisoft in celebration of the 25th anniversary of the Teenage Mutant Ninja Turtles in 2009. The game is a 4-player 2. 5D fighting game, similar to the Super Smash Bros. series. During battle, players attempt to KO opponents by depleting their life bar, knocking them off the stage or into traps. Characters are color-coded on-screen via a glow effect to help players keep track of their character (a feature that can be toggled on and off in the options screen). Like Super Smash Bros. , the game features many customizable options for battles. The game stresses interaction with the environment, and stages in the game feature traps, changes to the stage itself and interactive elements. The gameplay system also features items, including life-restoring pizza and ninja skills that grant players special abilities like fire breathing and electrical shields. The modes for this game are Arcade, Battle Royal, Survival, Tournament, Swap-Out, Practice, and Mission Mode, as well as an online mode for four players and mini-games. Players can collect 'shells' during battles or mini-games and use them to unlock special features, including trophies that other players can win in online tournaments. Arcade mode features animated cut scenes illustrated by Mirage Studios artists.

The plot involves Splinter holding a tournament for his sons, Casey Jones, and April O'Neil; Splinter himself also decides to join the tournament. After the winner is crowned, they are told to choose one trophy and something from Splinter's personal cabinet. However, suddenly, Professor Honeycutt calls them on the distress line, telling the Turtles that he has been kidnapped by the Shredder. Shredder breaks in on the communication and indicates that the line is not secure and taunts the Turtles, saying they won't retrieve Fugitoid. Pondering outside, Karai appears and says that the Shredder captured Fugitoid in order to force him to make a Transmat to teleport his armies all around the world. After defeating The Shredder, Karai reveals that she used the Turtles to get rid of the Shredder so she could usurp the Foot Clan from her father. Shredder stands back up, and Leonardo kicks him into Karai. Honeycutt flips the switch on the Transmat, which Shredder and Karai have landed on, and teleports them to parts unknown. Back in the sewer, Splinter presents the prizes to the tournament's victor. The game comes with a comic book that outlines the story further, up to prior to the Shredder's defeat. Scenes that were not in the game include Donatello rigging Renet's Time Scepter to transport them to Shredder's Tōkyō base, but it malfunctions and they zap across time, which provides an explanation for the bizarre stages such as the Old West and Japanese Castle. Upon their first teleporting with the Scepter, a giant alligator bursts through a sewer wall, which is accidentally transported to an Amazon rainforest, which explains why the gator stage hazard is in both the Sewer and Amazon stages. While at the Japanese Castle, the Turtles face an army of samurai, which turn out to be the Japanese demon known as Oni. The story ends after Fugitoid is rescued, and the Shredder appears for battle.