The zombie plague has struck the local college campus. Only a handful of brave cheerleaders are still fighting the endless wave of old comrades and professors turned into hungry, brainless creatures.

Zombies vs Cheerleaders is an asymmetrical two-player game in which one player controls the cheerleaders while the other player controls the zombies. The goal of the cheerleaders is to defeat all the zombies, while the goal of the zombies is to devour one of the cheerleaders.

The cheerleader are standing behind barricades and have powerful hand-made weapons and can attack with a certain strength. However, each time they attack, they lose energy. Once they run out of energy, they are knocked-out. Zombies have two characteristics: strength and protection. When they are hit by an attack greater than their protection they are removed from the game.

On their turn, the players have three actions they can spend to move their team or to attack. By killing bosses, cheerleaders can obtain special actions, while zombies can do the same by destroying the barricades.

The game uses illustrations made specially for the game by the design team of the comic book series "Zombies vs Cheerleaders".