"Kaiju Girl Caramelise" centers on Kuroe Aso, a shy and socially anxious high school girl who harbors a peculiar secret: she transforms into a kaiju, a giant monster, whenever she experiences intense emotions. This transformation is triggered by her feelings of embarrassment, stress, or attraction, often leading to chaotic and humorous situations. Kuroe struggles to control her monstrous alter ego while navigating the challenges of adolescence, including her growing feelings for her classmate, Arata Tani, who is oblivious to her condition.

The narrative explores Kuroe's attempts to balance her dual identity, as her kaiju form attracts unwanted attention from both the public and a secretive organization monitoring kaiju activity. As the story progresses, Kuroe learns more about the origins of her transformation, which ties into a larger mystery involving other individuals with similar abilities. The series blends elements of romance, comedy, and action, with Kuroe's kaiju form serving as both a source of conflict and a metaphor for her internal struggles with self-acceptance and emotional vulnerability.

Key characters include Arata Tani, a kind and supportive classmate who becomes a stabilizing presence in Kuroe's life, and Raku Kamiya, a mysterious girl with her own connection to the kaiju phenomenon. The interactions between these characters drive the plot forward, as Kuroe gradually gains confidence and begins to embrace her unique identity. The series balances lighthearted moments with deeper themes of identity, belonging, and the challenges of adolescence, all while maintaining a focus on Kuroe's journey toward self-discovery and emotional growth.