"3×3 Eyes" is a manga series that blends supernatural, adventure, and romance elements, centering on the journey of Yakumo Fujii, a young man whose life is irrevocably changed after encountering Pai, a mysterious girl with a third eye on her forehead. Pai is the last surviving member of the Sanjiyan Unkara, a race of immortal beings known as the Three-Eyed Ones. Her quest is to regain her humanity, a transformation that requires her to become human by transferring her immortality to another being. Yakumo becomes entangled in this quest when Pai accidentally makes him her immortal servant, or "Wu," after he dies protecting her. As a Wu, Yakumo gains immortality but is bound to Pai, reviving each time he dies unless Pai herself perishes.

The narrative unfolds as Yakumo and Pai travel across the globe, seeking a way to fulfill Pai's wish to become human. Their journey is fraught with danger as they encounter various supernatural entities, including demons, gods, and other Sanjiyan Unkara, many of whom harbor hostile intentions. The duo must navigate ancient myths, hidden relics, and powerful adversaries, all while uncovering the secrets of Pai's origins and the true nature of the Sanjiyan Unkara. Along the way, they form alliances with other characters, such as the demon hunter Benares and the scientist Dr. Minakami, who provide assistance and insight into the mystical forces at play.

As the story progresses, deeper layers of the Sanjiyan Unkara's history are revealed, including their connection to humanity and the catastrophic events that led to their near-extinction. Pai's character evolves from a seemingly naive and carefree girl into a more complex figure burdened by her past and the weight of her immortality. Yakumo, initially an ordinary young man, grows into a determined and selfless protector, driven by his loyalty to Pai and his desire to see her dream realized. Their relationship deepens, blending camaraderie, trust, and an undercurrent of romantic tension.

The series is marked by its intricate world-building, blending Eastern and Western mythological elements, and its exploration of themes such as immortality, identity, and the human condition. The plot is driven by a mix of action, mystery, and emotional stakes, with each arc revealing new challenges and revelations that propel the characters forward. The story culminates in a climactic confrontation that tests the limits of Yakumo and Pai's bond and resolves the central conflict surrounding Pai's quest for humanity. Throughout, "3×3 Eyes" maintains a balance between its supernatural elements and the personal struggles of its protagonists, creating a compelling and immersive narrative.