"ISUCA" is a supernatural action anime that centers on Shinichirō Asano, a high school student who moves to Tokyo to live with his aunt after his parents go missing. Struggling financially, he takes on a part-time job as a housekeeper for his classmate, Sakuya Shimazu, who comes from a family of demon-hunting exorcists. Sakuya possesses the ability to summon and control spirits, using her powers to combat malevolent entities known as "demons" that threaten humanity. Her unique technique, "ISUCA," involves sealing demons by calling out their true names.

As Shinichirō becomes entangled in Sakuya's world, he discovers that he has a rare ability called the "Eye of Providence," which allows him to see the true names of demons. This power makes him a valuable asset to Sakuya in her battles, but it also draws the attention of dangerous adversaries. The two form an uneasy partnership, with Shinichirō assisting Sakuya in her missions while navigating the complexities of their growing relationship.

The narrative explores themes of duty, sacrifice, and the blurred lines between humans and demons. Sakuya's stoic and disciplined demeanor contrasts with Shinichirō's more compassionate and impulsive nature, creating a dynamic that drives both the action and emotional arcs of the story. The series introduces various antagonists, including powerful demons and rival exorcists, who challenge the protagonists and test their resolve.

Throughout the series, the stakes escalate as Shinichirō and Sakuya face increasingly formidable foes, uncovering secrets about the origins of demons and the true nature of Sakuya's family legacy. The interplay between action, supernatural elements, and character development forms the core of the narrative, with a focus on the evolving bond between the two main characters as they confront the dangers of their shared world.