"Polyphonica Crimson S" is set in a world where music holds magical power, and humans coexist with spirits known as Muses. The story revolves around the Dantists, individuals who form contracts with Muses to perform magical music called "Polyphonica." These Dantists and their Muses work to maintain harmony between the human and spirit worlds, often resolving conflicts or anomalies caused by disruptions in the natural order.

The protagonist, Phoron Tatara, is a young Dantist studying at the prestigious Holy City of Akademia. He is partnered with Corticarte Apa Lagranges, a powerful and enigmatic Muse who often displays a cold and aloof demeanor. Despite their contrasting personalities, the two share a deep bond, rooted in a mysterious past that gradually unfolds throughout the series. Phoron’s journey is marked by his growth as a Dantist and his efforts to uncover the truth behind his connection to Corticarte, as well as the secrets of the Crimson Anniver, a legendary and dangerous musical score.

The narrative explores various episodic cases involving rogue spirits, corrupted music, and the misuse of Polyphonica, often leading to larger revelations about the world and its history. Key characters include Eufinley Tsuge, a skilled Dantist and Phoron’s rival, and her Muse, Aria, who provides a contrasting dynamic to Phoron and Corticarte’s partnership. The series also delves into the political and social structures of the Dantist society, highlighting the tensions between different factions and the ethical dilemmas surrounding the use of Polyphonica.

As the story progresses, Phoron and Corticarte confront increasingly complex challenges, culminating in a confrontation with the Crimson Anniver and its ties to their shared past. The series balances episodic storytelling with an overarching plot, blending action, mystery, and emotional depth. Themes of trust, sacrifice, and the transformative power of music are central to the narrative, as the characters navigate their relationships and the responsibilities of their roles as Dantists and Muses.