"Certain Magical Index" is set in a world where science and magic coexist, often in conflict. The story primarily unfolds in Academy City, a technologically advanced metropolis where students develop supernatural abilities known as "esper powers." The narrative centers on Toma Kamijo, a high school student with the unique ability to negate any supernatural power with his right hand, known as the "Imagine Breaker." Despite his seemingly weak power level, Toma frequently finds himself entangled in conflicts involving both scientific and magical factions.

The plot intertwines two major arcs: the science side and the magic side. On the science side, Academy City is a hub for esper development, governed by a secretive council that conducts experiments to push the boundaries of human potential. Toma becomes involved in various incidents, often protecting individuals targeted by these experiments. One such individual is Index, a young girl from the magic side who possesses the "Index Librorum Prohibitorum," a vast repository of forbidden magical knowledge implanted in her mind. Index becomes a central figure in Toma's life, and her presence draws him into conflicts with powerful magical organizations.

On the magic side, the story explores the intricate world of magical societies, including the Roman Catholic Church, the Anglican Church, and various occult groups. These factions often clash over the control of powerful artifacts or knowledge, with Toma frequently caught in the crossfire. His encounters with characters like Mikoto Misaka, a powerful electromaster, and Accelerator, the strongest esper in Academy City, further complicate his journey. Mikoto, in particular, becomes a recurring ally, while Accelerator evolves from a formidable antagonist to a complex anti-hero.

The series delves into themes of power, morality, and the consequences of human ambition. Toma's unwavering sense of justice and his willingness to protect others, regardless of the personal cost, drive much of the narrative. The interplay between science and magic serves as a backdrop for exploring the ethical dilemmas posed by both systems. The story is marked by its intricate world-building, with detailed explanations of esper abilities, magical rituals, and the political machinations of various factions.

As the series progresses, Toma's role expands beyond Academy City, involving him in global conflicts that threaten the balance between science and magic. His relationships with key characters deepen, and his actions have far-reaching consequences that ripple across both worlds. The narrative maintains a balance between episodic conflicts and overarching plotlines, ensuring a dynamic and engaging progression. Through its blend of action, mystery, and philosophical inquiry, "Certain Magical Index" presents a compelling exploration of a world where the boundaries between science and magic are constantly tested.