The focus of Ani-Mayhem is on exploration and comedic action, with a board-like Field randomly created by drawing special Location cards. The game employs screen captures from ten different anime franchises: Bubblegum Crisis, Tenchi Muyo!, Ranma ½, El-Hazard, Armitage III, Dominion Tank Police, Oh My Goddess!, Project A-ko, Phantom Quest Corp and Dragon Ball Z. The first four make up Set 0, while Set 1 is comprised of the following five, and Set 2 is entirely dedicated to Dragon Ball Z. Cards from all three sets are fully compatible with each other, although the rules from Set 2 (the latest one) supersede that of previous editions. Each player controls a team of four Characters (although this number may grow or decrease during play) in a quest to get a hold of the most Item cards. The game allows for any number of players and can even be played solo, thanks to the Disaster cards (representing villains or hazards) that must be activated when drawn or during a certain phase before players make their moves.
Players choose a four-Character Team then take turns randomly drawing from their Location cards and placing them face up to create the Field. Two Disasters and one Item are also drawn and placed under each Location card, face down. The goal is to win by collecting more than half Item cards in play, or possessing the most at the game's end. Each turn, players draw Power cards (Enhancements, Equipment, Flash Effects or Global Effects) to their hand, equip those usable by Characters, then move along the board as allowed by the Characters' Movement value. Skills listed on their cards let them Scavenge the Location they may reach; every locale has a requirement of Skills that must be met by the Team as a whole. Scavenging involves facing all Disasters placed therein, then collecting the Item below. Whenever Disasters remain face-up on the Field, play phases are preceded by a time where such Disasters must be controlled by all players (at this point, these cards mostly include villains with movement and fighting abilities like the heroes, whereas other Disasters represent obstacles). Both Combat Disasters and opposing Characters can be fought as Characters posses an Attack/Defense value, with the Combat card deck providing random modifiers to these values. The game ends when all Items have been collected/destroyed (since Disasters are capable of destroying Items) at which point the player holding the most is declared the winner; an instant win is also possible if one gathers more than half Items available. Disasters can "win" the game as well if a majority of Items is destroyed.
Dragon Ball characters playable in Ani-Mayhem include: Goku, Bulma, Yamcha, Master Roshi, Oolong, Chi-Chi, Ox-King, Krillin, Launch, Tien Shinhan, Chiaotzu, Baba, Piccolo, Yajirobe, Kami, Farmer with shotgun, Gohan, Bubbles, Gregory, Nail, Goten and Trunks. Variants such as "Baby Gohan" or "Gohan the Barbarian" exist, with alternate forms such as Super Saiyans also handled through separate cards. Vegeta, in his initial antagonistic role, can only be found as a Major Combat Disaster. Dragon Ball Item cards exist and allow for an alternative way to win the game when they are gathered. The Pure Heart Skill allows certain Characters to enjoy the Flying Nimbus Item card's various bonuses, though not all the right Characters are given this Skill (Krillin has it while Chi-Chi does not).
- Most of Set 2 takes its material from Dragon Ball Z's beginning up until the end of the Frieza Saga (including the corresponding movies). Character cards for Goten, Trunks and Future Trunks do exist, although their images are taken from the second Dragon Ball Z opening rather than an episode.