The player has a limited number of lives that gets depleted every time the player's energy gauge runs out. Two different 2-player modes are featured in the game, the first mode allows both players to hurt each other with their attacks, while the other mode disables this feature. The player can choose between any of the four turtles: Leonardo, Raphael, Michelangelo and Donatello, each wielding their signature weapon. Teenage Mutant Ninja Turtles III can be played by up to two players simultaneously, with each player controlling a different character. Taking April as his hostage, Shredder reveals that he has also turned the entire borough of Manhattan into a floating island and challenges the Turtles to come to his lair to stop him. While watching April O'Neil's latest news report, her broadcast is suddenly hijacked by the Turtles' nemesis, Shredder. The game begins with the Turtles spending their vacation in Key West, Florida. The game was re-released as part of Teenage Mutant Ninja Turtles: The Cowabunga Collection in 2022. It is based on the 1987 Teenage Mutant Ninja Turtles animated series, being released after the show's 5th season. The game features play mechanics similar to the previous game, Teenage Mutant Ninja Turtles II: The Arcade Game, but it is an original title for the NES without any preceding arcade version. It is the third video game iteration of the Teenage Mutant Ninja Turtles for the NES. Teenage Mutant Ninja Turtles III: The Manhattan Project is a side-scrolling beat-'em-up released by Konami for the Family Computer (Famicom) in Japan in 1991 and for the Nintendo Entertainment System in North America in 1992.

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