Nicktoons: Attack of the Toybots gameplay includes playing as two Nicktoons in some levels and plotting an operational Mech suit (created by Jimmy Neutron) in others. Players journey through Bikini Bottom, Amity Park, Fairy World, Pupununu Village (handheld version only), Retroville (handheld version only), and Calamitous' Lair (console version only), as well as the Toybot Factory, which is divided into multiple segments.
The opening intro for the game features Calamitous on some sort of game show (which is called the Biggest Genius). Professor Calamitous states that by feeding fairies Krabby Patties, they can emit a gas that, combined with Ghost energy, can be used as a form of fuel for his army of Toybots.
The game itself opens with Patrick Star and SpongeBob SquarePants delivering a truckload of several million Krabby Patties to a krabby patty processing and toybot factory. Upon arriving at the factory, a robot sucks up all the Krabby Patties, and Patrick, unintentionally, in the process. Spongebob chases after the robot, and eventually finds his way into the factory.
After finding his way through the factory, SpongeBob finds Patrick vacuum-packed like a toy. After freeing Patrick, he meets Tak, who claims to have been abducted and scanned. They later find Timmy and Jimmy, who also claim to have been abducted and scanned. They meet the Chad-Bot, a robot who is the Professor's helper. They ask him to use something to contact Danny Phantom and commands them to find more master models for his collection.
After collecting the master models, Jimmy contacts Danny, who says that Calamitous' invading toy army took over his house to use the energy coming from the Ghost Zone, so Jimmy tells Danny and Sam to meet him and the other Nicktoons at the Amity Park (which is almost destroyed) Evil Toy Co. Outlet and when they get there they see that Jimmy made some Mech-Suits that will let them fight the Big Tin Robots. After defeating a giant evil toy Jimmy head, they head back into the factory where they find some more master models.
Chad-Bot tells them that Sacer-Men toys capture heroes, so the Nicktoons go through the factory, collect the rest of the master of master models, and destroy the Saucer-Men toys. Then, the Nicktoons head to Fairy World. They then free Jorgen (who was in a frozen state on till Patrick bumped into him thanks to Jimmy), who destroys the fairly harvester, and then get back into the Mech-Suits to the Professor's lair (Jorgen even tells them to collect 500 fairies which they do).
They get to where the opening intro of the game was and the winner of the Biggest Genius is none other than Chad-Bot himself, who tells Calamitous' plan to abduct the best characters from every universe lead to his victory and the game ends with Chad-Bot cutting Calamitous' mustache off with an electric shaver.