The Syndicate was formed after Professor Finbarr Calamitous stole the blueprints of an inter-dimensional portal from his enemy Jimmy Neutron through a flea-bot on the brain of his robot dog Goddard. He used the portal to get access to different worlds and drain their energy with the help of each world's villain. Neutron then assembled the world's heroes (already knowing Crocker's enemy, Timmy Turner, from a previous incident) to fight the Syndicate and stop their draining. As they progressed through Amity Park, Bikini Bottom and the Fairy World, the group learned about the Syndicate's true plan: a Doomsday Machine with enough energy to destroy a whole world in seconds. Once the villains were defeated, Calamitous called them back to attack the heroes all at once. But even with the machine's defense system at full power, the group managed to defeat the Syndicate and shut the machine in time, sending their villains (each one trapped somehow) back to their home worlds.
Nicktoons: Globs of Doom
After Calamitous decided to follow other projects for world domination, another set of villains decided to take over the Syndicate. The new group was apparently led by Plankton, being the only returning member from the original group, while the other members included Ghost Zone resident Nicolai Technus, Calamitous' daughter Beautiful Gorgeous, and Pupununu sorcerer Tlaloc (from Tak and the Power of Juju, the newest sector of the Syndicate). During the Morphoids' attack, the heroes decided to join forces with the Syndicate, Zim and Dib also willing to help, though Dib volunteers to aid the Syndicate due to Zim lying his way onto the heroes' side.
Their combined might, along with a ship named the "Vessel of Portentia", is enough to stun the Morphoids' leader, Globulous Maximus. However, the villains (and Dib) betray the heroes (and Zim) and kick them out of the ship, planning to use Globulous for their own evil ends. However, Globulous changes sides and either (if he wins the final battle) defeats the villains, leaving them in the vacuum of space, or (if the villains win the final battle) gets defeated by them and put in a giant glass jar.
- Members - Professor Calamitous, Beautiful Gorgeous
- Type of energy - Electromagnetic energy
- Respective heroes - Jimmy Neutron
- Members - Vlad Plasmius, Nicolai Technus
- Type of energy - Ghost/ectoplasmic energy
- Respective heroes - Danny Phantom, Sam Manson, Tucker Foley
- Members - Denzel Q. Crocker
- Type of energy - Fairy/magical energy
- Respective heroes - Timmy Turner, Cosmo and Wanda
- Members - Sheldon J. Plankton
- Type of energy - Electric energy (through Jellyfish)
- Respective heroes - SpongeBob SquarePants, Patrick Star, Sandy Cheeks
- Dib Membrane is the only member of the group to not actually be a villain. As his nemesis Zim is on the heroes' side, it can be assumed Dib was placed on the Evil Syndicate to retain their protagonist/antagonist dynamic from the original series.