The protagonist genius, Ye Feng, was betrayed and attacked by his senior, and other evildoers, after he refines the Divine Realm pill that would lead him towards Supreme Realm. He managed to fend off and consume the pill, yet finds himself inhabiting the body of his descendant, who bears his name after 500 years later. He pledge to save his current lineage and seeks vengeance, Yefeng embarked on the path of cultivation again, practicing hard and improving while exploring the mystery of the way of heaven.

Reeling from her recent breakup, Momo Ayase, a popular high schooler, shows kindness to her socially awkward schoolmate, Ken Takakura, by standing up to his bullies. Ken misunderstands her intentions, believing he has made a new friend who shares his obsession with aliens and UFOs. However, Momo's own eccentric occult beliefs lie in the supernatural realm; she thinks aliens do not exist. A rivalry quickly brews as each becomes determined to prove the other wrong. Despite their initial clash over their opposing beliefs, Momo and Ken form an unexpected but intimate friendship, a bond forged in a series of supernatural battles and bizarre encounters with urban legends and paranormal entities. As both develop unique superhuman abilities, they learn to supplement each other's weaknesses, leading them to wonder if their newfound partnership may be about more than just survival.

Over a century ago, astral mages under persecution from the Empire banded together and established the Nebulis Sovereignty under three founding families: Lou, Hydra, and Zoa. With the leadership of Millavair Lou Nebulis VIII, the Sovereignty aims to minimize casualties in their conflict with the Empire—a stance the extremist Zoas disagree with. Tensions rise between the families as the upcoming election to decide the next leader approaches. The Zoas are willing to do anything to achieve success; however, a world-ending war may ensue should they be victorious. Princess Aliceliese "Alice" Lou Nebulis XI has no choice but to cooperate with any potential allies in order to advance towards her ultimate goal of ending the conflict that has long tormented everyone involved. This includes Iska—one of the Empire's greatest warriors and her greatest rival.

A young Taiwanese assassin codenamed "Glass Heart" committed suicide by jumping off a building, and her heart was pierced by metal fence. Miraculously, her life was saved by heart transplantation. During her recovery she began to experience strange dreams, which lead her to Japan looking for the donor of her heart, who happens to be Kaori Makimura, former partner of City Hunter Ryo Saeba. The author mentioned in the first tankoubon volume that Angel Heart only shares the same characters of City Hunter but not its continuation. The events are all parallel universe, therefore it has nothing to do with City Hunter.