It is the dark century and the people are suffering under the rule of the devil, Vandel, who is able to manipulate monsters. The Vandel Busters are a group of people who hunt these devils, and among them, the Zenon Squad is known to be the strongest busters on the continent. A young boy, Beet, dreams of joining the Zenon Squad. However, one day, as a result of Beet's fault, the Zenon squad was defeated by the devil, Beltose. The five dying busters sacrificed their life power into their five weapons, Saiga. After giving their weapons to Beet, they passed away. Years have passed since then and the young Vandel Buster, Beet, begins his adventure to carry out the Zenon Squad's will to put an end to the dark century.

Princess Rangiku lost her entire family to Lord Karimata, who invaded her home seeking her father's life work, puppets with unique capabilities. As her duty, Rangiku sets out with three of her father's greatest puppet warriors to seek revenge. She can manipulate these to battle the strongest of warriors, however manipulating the puppets leaves her own self vulnerable to direct attacks, so she seeks a ninja warrior named Manajiri to aid and protect her in her quest.

During the An Lushan Rebellion of the Tang Dynasty, monsters are everywhere and the people were destitute in the Central Plains. Li Haobai started from the Bashu and wanted to go to the front line to make a meritorious deed. On the way he was swallowed by the monster. By coincidence, Li Haobai and the guardian of the dragon’s veins merged with each other to obtain the power of the black dragon. And he has since been involved in the struggle of various forces.

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.