Misaki Sakura attends the same school as Noboru Takagami, situated in the parallel classroom next to his. She routinely visits his classroom during breaks, harboring deep romantic feelings for him. Though she actively observes Noboru, she remains too shy to confess. Their shared participation in the school's badminton club provides regular opportunities for interaction. Misaki's personality blends outward timidity with an intensely active internal imagination, causing her to frequently overanalyze situations and construct elaborate, often exaggerated scenarios.

This tendency escalates significantly after Kugen Tenko and Kou move into the Takagami household. Misaki consistently misinterprets Noboru's relationships with both newcomers, initially suspecting romantic involvement with either or both. Witnessing them together triggers spiraling imaginations, visible distress, and jealousy. While she eventually befriends Kou and ceases to view her as a romantic rival, Kugen Tenko's forward and unconventional behavior around Noboru continues to fluster her and fuel suspicion.

A pivotal event involves Kugen Tenko employing a hypnotic technique on Misaki. This temporarily transforms her into a powerful guardian to protect Noboru during a crisis. In this altered state, she displays unexpected combat prowess, such as forcefully intervening against a werewolf threat using a fire extinguisher. Misaki remains unconscious throughout the transformation and retains no memory of the incident afterward.

Her exposure to supernatural elements extends beyond this single incident. She witnesses conflicts involving entities like Shiro-chan and a Dema golem, during which characters like Enju warn her to flee for safety. Despite her ordinary human status and these encounters, her core role remains defined by unrequited feelings and imaginative anxieties, serving as a consistent source of comedy. Her name, Misaki (美咲), combines "beautiful" (美) and "blossom" (咲), while her surname Sakura (佐倉) incorporates "help/aid" (佐) and "warehouse/storehouse" (倉).

Her character background and development focus exclusively on her school life, unspoken affection for Noboru, and comedic reactions to the supernatural newcomers in his life, maintaining consistent dynamics throughout the series without substantial evolution.