Zombie Infection 2 is a horror-themed action game played from a bird's view perspective that has game mechanics similar to its predecessor. The game plays the same as the original Zombie Infection but it's more action oriented and has less emphasis on survival horror elements.

Taking place a year after the events of the first game, it sees Anderson, the hero of the original zombie outbreak, go to South America with a reporter (Keysha) only to see the undead rise again. Both characters are playable as is a native called Jeremi. The setting and some of the locations are similar to the series' smartphone entry but it has an original story and different characters.