Players take on the roles of familiar slapstick cartoon characters in Tom and Jerry in Fists of Furry. Gameplay follows traditional fighting games except that instead of mystic ninjas or street warrior champions, players choose to take on the role of Tom, Jerry, Spike, Duckling, or one of several other 3D rendered characters from the Tom and Jerry cartoons. In addition to the fists mentioned in the title, fighters can also use familiar household items like frying pans, drainpipes, and freshbaked pies as they step into one of the nine arenas to to battle.

Chen Chen returns to the international compound of China only to learn of his beloved teacher s death. This is compounded by the continual racist harassment by the Japanese population in the area. Unlike his friends, he confronts it head on with his mastery of martial arts while investigating his teacher s murder.