SpongeBob and Squidward are on their way to work when huge asteroids suddenly start raining down on Bikini Bottom. Squidward gets drenched in some orange goo that covers half of his face and makes him walk around like a zombie. As SpongeBob and Patrick panic at this, Jimmy Neutron then arrives and brings them to the Mawgu lair from Nicktoons: Battle for Volcano Island. There, they once again meet their teammates Danny Phantom and Tak (Timmy, Cosmo, and Wanda are inexplicably absent this time), along with their old foes, the Evil Syndicate, now consisting of Nicolai Technus, Beautiful Gorgeous, and Traloc, with Plankton as the only returning member. Also joining the party is Zim, who lies his way into joining the heroes, and Dib, who teams up with the Syndicate. They have joined up to stop the alien invaders, which are called Morphoids, when the Wise Old Crab arrives to inform them about the technology in the lair.
As Jimmy equips everyone with weapons befitting themselves, the two groups travel through Bikini Bottom until they eventually run into Bubble Bass, who turns into a giant zombie after eating a goo-covered Krabby Patty. After they defeat Bubble Bass by feeding him Krabby Patties, he vomits a large amount of goo onto SpongeBob. He is fortunately not mutated, but instead suddenly speaks in an evil voice when back at the lair getting washed of the goo, saying "Your world will end! My Globs of Doom will rain over your world... and take control!" The Wise Old Crab informs them that a huge robot called the Vessel of Portentia is hidden in the Mawgu Lair, and requires four special components to power it up.
The group then moves to Zim's town to find GIR playing with a taco that happens to be the Vessel's first component; he gets mutated by the goo and runs off with the component. After freeing Ms. Bitters, Gaz, and Professor Membrane, the protagonists catch up to the corrupted GIR, who eventually tires out of attacking them and is then returned. More goo lands on SpongeBob, who celebrates getting the component, but interrupts himself in the evil voice that now threatens it will be "smugglering" the planet. The group realizes that the Morphoids' leader is talking to them through a wavelength created by the goo that SpongeBob has absorbed.
Moving on to Amity Park, the group finds Morphoid asteroids raining on the citizens, including the now-freed Ghost Dog, who starts rampaging through town. After freeing Dash, Tucker, and Jazz, the heroes and villains battle the Ghost Dog at a power plant and soon gain another piece of the Vessel. Once returning to the Mawgu Lair, the Morphoids' leader reveals himself to be named Globulous Maximus through SpongeBob.
Heading to Retroville, the group finds that Jimmy's girl-eating plant has become a monstrous giant thanks to the goo. After defeating several more Morphoids and freeing Carl, Cindy, and Sheen, they fight the girl-eating plant at the mall and retrieve the third piece of the Vessel. SpongeBob, after getting covered in the goo again, tells the group that Globulous Maximus is only a few light-years away from Earth and is preparing to send more gigantic Morphoids to destroy it.
The group's last stop is Pupununu Village, where they find the last component of the Vessel covered in goo and freeing Jibolba and Jeera. SpongeBob pokes the goo to try and free the component, and sure enough, gets covered in goo. He grabs the component and races to the Mawgu Lair.
Having collected all the pieces of the Vessel of Portentia, the two groups head out into space to defeat Globulous Maximus. Just as they have done so, however, the Evil Syndicate (and Dib) betray the heroes to capture Globulous for their own evil plans, taking over the Vessel of Portentia and ejecting the heroes (and Zim). Globulous admits to the heroes that he has only been destroying worlds because he wasn't happy with his form, having been created by the Big Sneeze that created their universe. SpongeBob tells him he should embrace who (or what) he is, and afterward, Globulous offers to help them stop the Syndicate, turning himself into a huge, orange, cycloptic version of SpongeBob. Depending on the player's actions, one of two endings will occur.
In the "good" ending, achieved by simply defeating the final boss, Globulous and the heroes manage to defeat the Vessel of Portentia on the moon, and it explodes in space, leaving the villains floating around. Globulous returns the heroes to Earth, and says that he will right the wrongs in the universe by taking the moniker "SpongeGlob". The heroes bid him farewell, and SpongeGlob blasts off into space. Meanwhile, SpongeBob sneezes, and the goo finally exits from his body through his many holes. Patrick compares this moment to the beginning of the universe where SpongeGlob was born, while the Wise Old Crab then summons a typical "The End" sign.
In the "alternate" ending, which requires having a second player take control of the villains' robot on a file that has not already been completed and defeating the first player, Globulous, the villains are shown to have captured Globulous in a giant glass jar, with the credits rolling immediately afterwards.
- Encyclopedia SpongeBobia: SpongeBob SquarePants featuring Nicktoons: Globs of Doom
- Jimmy Neutron Wiki: SpongeBob SquarePants featuring Nicktoons: Globs of Doom
- Danny Phantom Wiki: SpongeBob SquarePants featuring Nicktoons: Globs of Doom
- Invader Zim Wiki: SpongeBob SquarePants featuring Nicktoons: Globs of Doom
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