Misaki Saiki has albinism, granting her white hair, pale skin, and red eyes, along with vision impairment requiring corrective glasses. This condition led to childhood ostracization and loneliness as classmates ridiculed her appearance. Her psychic abilities emerged early, though she concealed them. Her parents divorced; her mother vanished post-separation and her father, Shigeyuki Saiki, became emotionally distant. She resided primarily with her grandmother, though details about this relationship are limited.

Professionally, she holds dual roles. She works as a dominatrix at the Roppongi Myure Mule S&M club, serving clients' BDSM requests and excelling in this field. This occupation attracts obsessive admirers, notably Mitsuru Fujiwara, who stalks her. Concurrently, she serves as a necromancer for the Livelihood Preservation Group, a government agency. In this role, she perceives, communicates with, and exorcises ghosts, often guiding them onward. She utilizes a demonic familiar named Kinue—manifesting as a sentient, hair-braided rope—which subdues spirits and requires periodic feeding on humans. Paradoxically, despite her involvement in sex work, she maintains her virginity and views her necromancy duties as more morally tawdry than her dominatrix work.

Her character evolves through collaborations with colleagues and encounters with spirits. She partners with Souichiro Kadotake, a martial artist aiding her missions despite his severe fear of ghosts. Their investigations frequently involve resolving traumatic events tied to spirits, such as aiding Ai Kunugi—a middle school student whose sister and niece died tragically. Misaki becomes Ai's reluctant mentor after helping her uncover the truth behind their deaths, fostering Ai's own nascent psychic abilities. These cases expose societal issues like suicide culture, sexual abuse, and exploitation. Her approach to spirits blends pragmatism with unexpected empathy, as seen when she risked suicide to pacify a bridge spirit embodying profound loneliness, though she employed deception to survive.

Key traits include cynicism stemming from her troubled past, yet she demonstrates fiercely protective instincts, particularly toward Ai. She exhibits discomfort with her albinism-related features, such as her lack of pubic hair, and avoids sunlight, sensitive to its glare. Her grandmother's teachings occasionally surface, such as showing reverence for bindweed despite her abrasive demeanor. Ongoing struggles involve balancing her professions, managing Mitsuru's stalking, and confronting spirits influenced by carnal or violent unresolved issues, reflecting her internal battles with isolation and societal marginalization.