The Powerpuff Girls and their friends travel to New York and meet a young man named Peter Parker, who gains spider powers after being bitten by a radioactive spider during a class trip. He dons the identity of Spider-Man as he, along with Team Powerpuff and some Loud allies, must save New York from the terror of the Green Goblin, Mojo Jojo, and Dr. Eggman.
The Powerpuff Girls: Blossom, Bubbles, & Buttercup
The Chipmunks: Alvin, Simon, & Theodore
Garfield & Odie
The Teenage Mutant Ninja Turtles: Leonardo, Donatello, Raphael, & Michelangelo
Yoshino Fujieda & Lalamon
Sonic the Hedgehog & Miles "Tails" Prower
The Loud Kids: Lincoln, Lori, Leni, Luna, Luan, Lynn, Lucy, Lola, Lana, Lisa, & Lily
- The music will be from Danny Elfman and John Powell while the additional music will be from Heitor Pereria and Michael Giacchino
- The theme will be composed by Danny Elfman (from Spider Man 1&2) and Michael Giacchino (from Spider-Man: Homecoming)
A sequel, The Powerpuff Girls Meet Spider-Man 2 has been announced by KirbyStar Studios and wil be in production before Spider-Man: Homecoming starts.