Misa Kuroi is a witch who has long since grown tired of her immortality. After centuries of existing on the fringes of human society, she now runs a small, unassuming apothecary shop in a modern Japanese city, where she sells mundane remedies and the occasional genuine charm to unsuspecting customers. Her true occupation, however, is the collection and disposal of cursed objects, lingering grudges, and supernatural maladies that ordinary people cannot see. She is cynical, world-weary, and blunt, but she adheres to a strict personal code: she will help those who genuinely seek her out, but she never forces her aid upon anyone.

The central conflict arises when a high school student named Yuto Aoki stumbles into her shop, carrying a family heirloom that has begun to manifest violent, reality-warping curses. Unlike most clients, Yuto can see the true form of the curse, a rare ability that marks him as a potential medium. Misa reluctantly takes him on as a part-time assistant, not out of kindness, but because his presence seems to attract a particular kind of high-grade spiritual pollution that she finds useful for her own research. Their relationship is transactional at first, but as they encounter a series of cases, a deeper mystery unfolds: the curses they face are not random. They are fragments of a single, ancient calamity that Misa herself was involved in during the witch hunts of the 16th century.

The narrative is structured as a monster-of-the-week procedural that slowly builds into an overarching saga. Early arcs focus on self-contained stories, such as a cursed mirror that traps the vain, a bracelet that feeds on romantic jealousy, and a stray cat that acts as a vessel for a vengeful spirit. Through these cases, Yuto learns the rules of Misa’s world, including the cost of using magic, which slowly erodes the user's humanity. Concurrently, Misa’s past is revealed in fragments. She was once a member of a coven that sought to create a utopia by severing all human negativity, but their ritual backfired, creating a sentient "core curse" that absorbed their power and scattered across the world. Misa was cursed with immortality as punishment for her role in the failure.

The major turning point comes when Yuto is gravely injured by a curse that mimics Misa’s own signature magic. This forces her to confront that her past is not just a memory but an active pursuer. The core curse has begun to reassemble itself, and it is targeting her surviving coven members one by one. In the second half of the series, the duo is joined by other survivors and antagonists, including a pragmatic exorcist who uses technology and a rogue witch who believes the core curse should be reawakened to complete its original purpose. Misa must decide whether to find a way to finally die, or to live long enough to destroy the monster she helped create, while Yuto struggles with his growing attachment to a woman who is fundamentally disconnected from human life spans. The story culminates in a confrontation where Misa is forced to sacrifice her accumulated centuries of memories to seal the core curse, leaving her alive but as a blank slate, with Yuto taking on the role of her guide in a new, uncertain life.