The series is set in the mechanical city of Edoropolis (a portmanteau of "Edo" and "metropolis", called "Little Tokyo" in the dub) is a mechanical city which fuses feudal Japanese culture with 1990s culture and is populated by cybernetic anthropomorphic "animaloids", or animal androids. The city is notionally led by Shogun Iei-Iei Tokugawa ("Emperor Fred" in the dub), but as he is a doddering eccentric, the city's actual leadership lies in the hands of his daughter Tokugawa Usako (Princess Violet) and a council headed by the ambitious prime minister Kitsunezuka Ko'on-no-Kami (Seymour "The Big" Cheese; identified as a fox in the original, but a rat in the dub), who constantly plots to overthrow the Shogun with the help of his trusted advisor Karasu Gennarisai (Jerry Atric), and Karamaru (Bad Bird), the leader of an army of ninja crows.
Unknown to the prime minister, council member Inuyama Wanko-no-Kami (Big Al Dente), the commander of the Palace Guard, learns of his designs on leadership, but is unable to prosecute him for treason because of the plausible deniability he maintains. Instead, Inuyama enlists the services of Yattarou (Speedy Cerviche), Pururun (Polly Esther), Sukashii (Guido Anchovy) and their operator Otama (Francine), four cyborg cat ninjas (samurai in the dub) who work in the city's pizzeria. Also known as the Nyankii, they are assigned to to stop Kitsunezuka Ko'on-no-Kami and his evil henchmen's plans to take over Edoropolis.