Worms 4: Mayhem is a sequel to Worms 3D. Like its predecessor, it is a turn-based artillery variant with humorous themes and weapons, in which players control small armies of worms. The gameplay is similar to that of the previous game, adding a more developed Story mode, in which the player cooperates with the wise Professor Worminkle, who can use a time machine to travel to different time periods such as American Old West, ancient Arabia, and Prehistoric Age.

In this installment, players can customize the appearance of their worms, including helmets, glasses, facial hair, gloves, etc. A new mode called "Weapon Factory" has been added, allowing players to forge their own weapons. The game also contains a shop where players can purchase various items, using points accumulated by completing story missions or unlocking trophies. Shop items include new maps, accessories, outfits, character voices, etc.