In the game, the player controls Jimmy in a quest to save Earth from the alien "Twonkies" using gadgets and inventions. Although made after the Jimmy Neutron episode, "Attack of the Twonkies!", levels are designed with the same mechanics as the film, including a rocket and the theme park "Retroland".
The game starts with Jimmy in a classroom, and they talk about a comet coming in close orbit of the Earth, Jimmy takes a rocket ship there and ends up finding alien life, which he accidentally brings back with him.
The game features multiple boss fights and features putting together random objects into one invention that assist in defeating bosses and collecting Twonkies.