"Hijitsuzai Suiri Shōjo A-ya" centers on Aya, a high school girl with a unique ability to perceive and interact with the "invisible" world—entities and phenomena that exist beyond ordinary human perception. This ability, while granting her insight into mysteries and supernatural occurrences, also isolates her from her peers, as she struggles to balance her dual existence between the visible and invisible realms. The narrative unfolds as Aya becomes entangled in a series of bizarre and often unsettling incidents, using her skills to uncover hidden truths and solve enigmatic cases.

The story is structured around episodic mysteries, each presenting a new supernatural or psychological puzzle. Aya's investigations often involve deciphering the motives and histories of spirits, ghosts, or otherworldly beings, as well as unraveling the human emotions and tragedies tied to these phenomena. Her interactions with these entities reveal deeper layers of the invisible world, which operates under its own set of rules and logic. Alongside her is a small group of allies, including classmates and acquaintances who, while initially skeptical, gradually come to acknowledge and assist her in her endeavors.

Aya's character is defined by her sharp intellect, emotional resilience, and a sense of duty to help both the living and the dead. Her ability to perceive the invisible is not portrayed as a mere plot device but as a burden she must bear, often leading to personal sacrifices and moral dilemmas. The series explores themes of loneliness, the nature of reality, and the thin boundary between the seen and unseen, blending elements of mystery, horror, and psychological drama.

The plot progresses through a mix of self-contained cases and overarching storylines, with certain mysteries hinting at larger, interconnected events. As Aya delves deeper into the invisible world, she uncovers secrets about her own past and the origins of her abilities, adding a layer of personal stakes to her investigations. The series maintains a balance between supernatural intrigue and character-driven storytelling, with Aya's growth and relationships serving as a focal point amidst the eerie and often unsettling atmosphere.