Eterno follows the story of Rhea, a curious, lively and practical Angel who attends the Aurum School in order to become a fully fledged Guardian Angel. All sixteen-year-old students in Heaven have an annual ceremony where they acquire their wings and undergo a Heavenly Dust induced aptitude test that reveals their best-suited element based on their personality and history. Afterwards, they are categorized into five groups: Air, Light, Water, Earth and Mind, with one secret group known as Aester, which possesses attributes of multiple elements. The Angels of this group are believed to be extinct and are referred to as Supreme Guardians.

At her sixteenth birthday ceremony, Rhea acquires her wings but doesn't finish her aptitude test as the school gets infiltrated by Demons. In her attempt to save her friend from being attacked by the intruders, Rhea gets caught and abducted herself. Suddenly plunged into a life of adventure as she tries to discover what happened to her, Rhea sets off on a journey to find answers across the nightmarish landscape of her enemies. One of the high-ranking Demons, Kato, shows unusual interest in her and spares her life. For the next six days, Rhea learns to coexist with him, following his rules to survive while looking for a way to escape. Eventually, she is faced with shocking realizations about her powers as she is a Supreme Guardian, the most powerful kind of Angel in the entire dimension. By then, her relationship with Kato develops, and she is confronted with her biggest fear: falling in love with him.