Serious Sam: Kamikaze Attack is a 2D game where the player is a Beheaded Kamikaze and must chase Serious Sam to blow him up. Sam has several weapons, such as a rocket launcher or tossing Serious Bombs, which he will use to destroy the Kamikaze. If they hit the Kamikaze, he will die. The Kamikaze can jump over projectiles, or kick them away if they're getting too close. However, the Kamikaze has a rage meter which will increase whenever he kicks. If the meter gets too high, he will explode, which will take away one of the Kamikaze's lives. If the Kamikaze runs out of lives, the player will lose and have to restart from the beginning. There is also a point system, which rewards the player for things like kicking back projectiles and killing Sam.

The levels take place in locations such as a desert and a forest. There are also challenge levels that test the player's skills, which are good for those that have completed the basic game and want more out of it.

The player can buy and wear heads for the Beheaded Kamikaze, which will change various attributes of him, such as changing the rage meter penalty for when the Kamikaze kicks a projectile away. These hats represent various characters in the Serious Sam series, such as the Sirian Werebull and the Kleer Skeleton.