The Teenage Mutant Ninja Turtles are taking a break in the sun, watching the news about the rising crime rates in New York City. Suddenly, their TV signal is hijacked by Shredder, who appears on the screen with a message for the turtle friends. He lifts the entire Manhattan island into the sky and takes April as a hostage. Witnessing this, the Teenage Mutant Ninja Turtles must fight through waves of enemies to make their way back home and save April and the city. So, if you don't want Shredder to throw sand in your face and take your best girl and hometown away, you better get to it.

The Manhattan Project is a sequel to the Teenage Mutant Ninja Turtles II arcade game. The third game in the series is very similar to the second. The player selects one of the main turtles, who must fight through stages, kill as many soldiers as possible, face and defeat bosses, and ultimately fight Shredder. Unlike the previous game, each turtle hero has their own unique abilities.