They arrive in Vlad's new castle by accident, where he reveals his ghost portal is syphoning energy from the Ghost Zone to further the Syndicate's plans. As a precaution, Vlad captured Danny's parents. Vlad knocks them out and imprisons in the Ghost Zone Prison. Befriending the Box Ghost, the heroes escape after knocking out Walker. Danny leads the heroes to the Fenton Works ghost portal, where he claims no relation to the Fentons and that they're Ghost Hunter experts. They meet Danny's friends, Sam and Tucker, who explain some ghost have possessed the citizens. Danny drives out the ghosts, before the group cuts through the Amity Park Graveyard to Vlad's castle. Upon arrival, Jimmy realizes there're generators keeping the portal open. They destroy the generators, shutting off the portal. Confronting Vlad, Danny possesses his dad Jack, using the 'Ghost Gauntlets' to pummel Vlad. Vlad gloats the Syndicate is building something and have sufficient ghost energy to help power it before fleeing.
They next arrive in Bikini Bottom (with Jimmy, Danny, and Timmy using Jimmy's air gum to breathe underwater). They meet Sandy, who explains Plankton uses harvesters to capture jellyfish to extract power from their sting; he also captured Mr. Krabs. Sandy sends them to Jellyfish Fields to meet Patrick, but he's sucked into a harvester. Destroying the harvesters, the group find themselves on the Flying Dutchman's ship; they (minus SpongeBob since he's annoying) are to be his new crew. However, Danny persuades him to let them go in exchange for bringing back his old crew. Arriving at the Chum Bucket, they free Patrick and the jellyfish. On the roof, they face Plankton (using a robot crab) and rescue Mr. Krabs. The heroes learn the Syndicate is extracting energy for a Doomsday Device, and Crocker is still supplying power to it.
In Dimmsdale, the heroes infiltrate Crocker's golden fortress, finding a rainbow of Fairy Magic ending there. After reactivating the prisim, they arrive in Fairy World. Since Jimmy has been here before, he gives an incorrect explanation. Jorgen explains Crocker is extracting the magic from the Big Wand to feed the Doomsday Machine. After freeing the fairies, they go to The Big Wand, where they defeat Crocker. SpongeBob and Danny deduce the villains are retreating to Retroville to regroup after being defeated. Timmy believes everything will okay with the Big Wand giving fairies back their full magic, by wishing the bad guys into jail and the dismantling of the Doomsday machine. However, Wanda says Da Rules only allow changes to Dimmsdale's dimension, disappointing the heroes.
They return to Jimmy's lab, where Calamitous contacts them, saying the Doomsday Machine is almost finished. SpongeBob sees Goddard scratching his ear, making Jimmy realize Calamitous planted a flea-bot in Goddard to spy on him. They shrink down and enter Goddard, defeating the flea-bot; Jimmy uses the flea-bot's circuitry to locate Calamitous' lair. Upon arrival, the Syndicate declares the world will be destroyed as a show of power; the machine will shield them. Despite the heroes damaging the machine, the villains continue the count down. SpongeBob unplugs the Doomsday Machine; Calamitous laments he forgot a back-up system.
With Calamitous arrested, the heroes part ways. Jimmy gives each a Neutronic Recallers in case of a future repeat. SpongeBob leaves first, most likely holding Plankton captive in his pocket. Danny gives Jimmy a second Fenton Thermos (since Vlad is trapped in the original), which Jimmy thinks will help him figure out what "those phantasmol images really were". Timmy thanks Jimmy for a Hyber-Cube, which is holding Crocker captive. Cindy waves Timmy off. After this, Jimmy says a familiar line: "Cindy, get out of my lab!"
In the console version, the player can play with three computers and no other human players, or with a friend or two with the remaining computer(s). One can switch abilities, which have multiple uses. There are also things only a certain character can do. For example, SpongeBob is needed to use Bubble Bombs to blow up a pillar, Danny is needed to use Ghostly Wail on some glass, Timmy is needed to use Freeze Glove to freeze some water, or Jimmy has to shoot down some things with his Neutron Flare.
Goddard can be found in all four worlds (and oddly enough, inside himself) so he can upgrade the players weapons and abilities.