One player controls the Powerpuff Girls, trying to stop Mojo Jojo from using his laser tower to destroy them and Townsville. The other player controls Mojo Jojo, trying to take out the Powerpuff Girls. Each character has an individual deck of action cards. Players try to reduce opposing characters' hit points to KABLOOEY! The Powerpuff Girls player selects a girl to activate and draws from the appropriate deck. The player will then follow the card instructions (usually movement). If the girl moves adjacent to Mojo Jojo, then she can fight him along with any other girls that are with her. Fighting Mojo Jojo consists of rolling one die for each girl in the fight. Each die has 3 sides with no stars, 2 with one star and 1 side with two stars. For each star rolled, Mojo Jojo loses one hit point. The Mojo Jojo player draws a card from the Mojo Jojo deck and follows the instructions. Mojo Jojo may attack if adjacent to a Powerpuff Girl, rolling a black die that is the counterpart to the girls' dice, except with splats instead of stars. Then Mojo Jojo gets a second attack. The player throws a red die through the laser sight on the 3D Laser Tower to physically knock down one or more of the Powerpuff Girl figures. Each girl knocked down loses a hit point. A Powerpuff Girl whose hit points are reduced to KABLOOEY! is out of the game and her figure and deck are removed. Mojo Jojo wins if all three Powerpuff Girls are removed from the game. The Powerpuff Girls win if Mojo Jojo's hit points are reduced to KABLOOEY!