The Trading Card Game revolves around the collecting of two core sets of trading cards. Unlike in reality where most trading cards are obtained through booster packs or similar packaging, trading cards in No More Heroes are obtained from chests, or by unearthing them from particular sections of Santa Destroy where they are buried. There are two obtainable sets in the game, Mask of the Legendary Wrestler and Design Materials, though cards from the latter set are only available after starting a New Game +.

During the first playthrough of No More Heroes, there is only one obtainable set in which each card represents the same thing – the mask of a popular, "legendary" lucha libre wrestler. During the second playthrough however, new cards from a second set begin to appear, each of them featuring different types of concept art from the game, including character designs, expressions, weapons, profile cards, and art of several other things surrounding the game, including Pure White Lover Bizarre Jelly.