"Mieruko-chan" centers on Miko Yotsuya, a high school girl who suddenly gains the ability to see horrifying and grotesque spirits that are invisible to others. These spirits, ranging from unsettling to outright terrifying, appear in her daily life, often in mundane settings like her school, home, or public spaces. Despite her fear, Miko chooses to ignore these apparitions, believing that acknowledging them might provoke their hostility or draw unwanted attention. Her strategy is to maintain a calm demeanor, pretending not to see them, even as they grow increasingly intrusive and menacing.

Miko’s life becomes more complicated as she encounters other characters who are either aware of or connected to the supernatural world. Her best friend, Hana Yurikawa, remains oblivious to the spirits but provides emotional support, often unintentionally putting Miko in precarious situations due to her cheerful and carefree nature. Another key figure is Romm, a mysterious man who runs a shrine and seems to possess knowledge about the spirits and how to deal with them. His presence introduces a deeper layer to the narrative, hinting at a larger supernatural framework and potential ways to confront the entities Miko encounters.

The series balances horror with dark comedy, as Miko’s attempts to ignore the spirits often lead to absurd or tense situations. The spirits themselves vary in design and behavior, with some being passive observers and others actively seeking to harm or manipulate those around them. Over time, Miko’s resolve is tested as she faces increasingly dangerous encounters, forcing her to consider whether her strategy of avoidance is sustainable.

The narrative explores themes of fear, resilience, and the unknown, as Miko navigates her dual reality of ordinary life and supernatural terror. The story gradually reveals more about the nature of the spirits and the reasons behind Miko’s ability, intertwining her personal struggles with the broader mysteries of the spirit world. The series maintains a steady pace, blending episodic encounters with a developing overarching plot, keeping the tension and intrigue consistent throughout.