Nicktoons: Underwater Rescue is the sequel to Nicktoons Unite!, Nicktoons: Battle for Volcano Island, Nicktoons: Attack of the Toybots and Nicktoons: Globs of Doom. Characters from SpongeBob SquarePants, Danny Phantom, The Adventures of Jimmy Neutron: Boy Genius, Tak and the Power of Juju and The Fairly OddParents appear.
While relaxing in the water park, the Nicktoons Heroes hear a young damsel-in-distress screaming for help. They also realized that the damsel-in-distress is Danny's sister, Jazz! She has been captured by the Evil Syndicate and being taken to one of the water slides that have a portal inside. Now, it's up to the heroes to rescue her and stop the Syndicate from vaccuming all the water.