"Nyanpire - The Vampire Cat" centers on a stray black cat who is saved from near-death by a vampire. The vampire bestows his blood upon the cat, transforming it into a "nyanpire"—a vampire cat. The cat, now named Nyanpire, retains some vampiric traits, such as a thirst for blood and a tendency to say "knyaa" (a cat-like version of "nya") instead of "kyaa" (a typical vampire sound). Despite these traits, Nyanpire is more cute and comedic than menacing, often relying on his human caretaker, Misaki, for support.

Misaki is a kind-hearted young girl who adopts Nyanpire after he wanders into her home. She provides him with blood in the form of fish-shaped blood packs, which he consumes eagerly. Nyanpire becomes deeply attached to Misaki, often expressing his affection in playful and endearing ways. The series explores their daily life together, blending slice-of-life elements with supernatural themes. Nyanpire's interactions with other animals and humans, including a rival cat named Chachamaru, add humor and lightheartedness to the story.

The narrative does not follow a heavily serialized plot but instead focuses on episodic adventures and comedic situations. Nyanpire's vampiric nature is often played for laughs, as he struggles with his small size and lack of intimidating presence. Despite his limitations, he occasionally displays moments of bravery and loyalty, particularly when Misaki is involved. The series maintains a light tone throughout, emphasizing the bond between Nyanpire and Misaki while incorporating whimsical elements of the supernatural. The characters' relationships and Nyanpire's quirky personality drive the story, creating a charming and humorous viewing experience.