"Gregory Horror Show" is a surreal and darkly comedic anime series set in the eerie confines of Gregory House, a mysterious hotel that serves as a purgatorial trap for its guests. The protagonist, a nameless traveler, becomes stranded at the hotel after losing their way. Gregory, the eccentric and unsettling proprietor, informs the guest that the only way to leave is to collect "lost souls" hidden throughout the hotel. These souls are represented as small, glowing orbs, and their retrieval becomes the central objective of the story.

The hotel is populated by a bizarre and macabre cast of characters, each with their own distinct quirks and unsettling personalities. Among them are Catherine, a vampiric nurse who wields a giant syringe; James, a chainsaw-wielding rabbit obsessed with cleanliness; and Hell's Chef, a demonic cook who serves grotesque meals. These characters often hinder or assist the protagonist in their quest, creating a series of episodic challenges that blend horror, humor, and psychological tension.

As the protagonist navigates the labyrinthine corridors of Gregory House, they encounter increasingly surreal and disturbing scenarios. The hotel itself seems to shift and change, defying logic and trapping the protagonist in a nightmarish loop. The narrative explores themes of guilt, regret, and the consequences of one's actions, as the lost souls often represent the protagonist's own inner turmoil and unresolved emotions.

The series is structured as a series of vignettes, with each episode focusing on a specific character or challenge within the hotel. The tone oscillates between dark comedy and genuine horror, creating a unique and unsettling atmosphere. The minimalist animation style, characterized by its stop-motion aesthetic, enhances the surreal and otherworldly quality of the story.

Ultimately, "Gregory Horror Show" is a psychological journey through a twisted and symbolic landscape, where the protagonist must confront both external obstacles and their own inner demons. The series leaves much open to interpretation, with its ambiguous ending and cryptic narrative elements inviting viewers to draw their own conclusions about the nature of Gregory House and the fate of its inhabitants.