Many years have passed since humanity vanished from Earth, leaving the planet to be reclaimed by nature. In Tokyo's Ginza district, the Gingarou Hotel continues to operate as if nothing has changed, kept running by its remaining robot staff. The central figure is Yachiyo, a hotelier robot who acts as the acting manager, alongside other functional robots like the Doorman Robot and the Environment Checker Robot. They have been waiting for the hotel's owner to return and for human guests to finally walk through their doors again.

A century after humanity's departure, the first visitor finally arrives—but it is not a human, but an extraterrestrial. This marks the beginning of a new era for the hotel, as a succession of alien guests begin to appear. Among the most significant arrivals is a family of tanuki-like aliens fleeing a war on their home planet. They settle on Earth, converting their spaceship into a home, and one of the tanuki, Ponko, eventually joins the hotel staff. Thanks to the tanuki's long lifespans, Yachiyo and Ponko work together for centuries, gradually improving the hotel and attracting more alien visitors.

Apocalypse Hotel Karikari is a direct sequel to the earlier manga Apocalypse Hotel Pusupusu, both original comic adaptations based on the anime series. While the anime follows a continuous timeline covering hundreds of years, this manga takes an episodic approach, with each self-contained chapter focusing on a single absurd or heartwarming incident not fully explored in the main story. The tone remains comedic and slice-of-life, with the robots' unwavering dedication to hospitality colliding with the unpredictable and often bizarre behavior of their alien guests. Despite the post-apocalyptic setting, the narrative emphasizes humor, small daily dramas, and the quiet determination of machines waiting for a humanity that may never return.