"Haiyoru! Nyaruani" is a surreal comedy anime that blends absurd humor with cosmic horror, centered around the daily life of Nyarlathotep, a chaotic deity from the Cthulhu Mythos. Nyarlathotep, often referred to as Nyarko, takes on the form of a silver-haired girl and moves in with a high school student named Mahiro Yasaka. Mahiro, a self-proclaimed ordinary teenager, becomes the unwilling target of Nyarko's relentless affection and bizarre antics. Despite his attempts to maintain a normal life, Mahiro is constantly dragged into Nyarko's chaotic world, which includes her rival, Cthugha, another cosmic entity who also takes on a human-like form.

The series unfolds as a series of episodic, slice-of-life scenarios, with Nyarko and her friends engaging in over-the-top, often nonsensical situations. These range from mundane activities like cooking and shopping to more fantastical events involving alien invasions, interdimensional travel, and battles with otherworldly beings. Nyarko's obsession with Mahiro and her attempts to win his affection are a recurring theme, often leading to comedic misunderstandings and exaggerated conflicts.

Supporting characters include Hasuta, a space detective who resembles a small, fluffy creature, and Kuko, a fiery deity who frequently clashes with Nyarko. The interactions between these characters are marked by rapid-fire dialogue, slapstick humor, and frequent references to Lovecraftian lore, though the tone remains lighthearted and comedic rather than dark or serious. The series thrives on its absurdity, blending mundane human experiences with the incomprehensible nature of cosmic entities, creating a unique and often unpredictable narrative.