The story of El Shaddai: Ascension of the Metatron takes place in a fantastical interpretation of biblical themes, inspired by the apocryphal Book of Enoch. God sends Enoch on a mission to capture angels that have fallen short of their duties to watch over humanity. These angels, called Grigori, became fascinated with humans and renounced Heaven to live among them. Enoch must navigate their realms, battle their aberrant Nephilim offspring, find the fallen angels, and bring them back to Heaven's fold.