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Darling in the Franxx takes place in a dystopian, post-apocalyptic future where the remnants of human civilization have abandoned the surface. Adults and children exist in contrasting environments from each other. Adults live in technologically-advanced cities within Plantations and are immortal, but procreation and relationships among them have become obsolete and undesirable. Artificially-created children, termed "parasites", are deprived of individuality and are educated only for piloting Franxx in pairs to defend humanity. Parasites are kept in isolation from adult society in environments nicknamed "birdcages", which emulate that of a bygone era, so that they can develop the emotional responses required to pilot a Franxx.

In the early 21st century, the progress of human civilization was accelerated by ground-breaking discoveries in mining technology, allowing extraction of magma energy for a new low-cost, all-encompassing energy source. Scientists contributing to the breakthrough formed "APE", an organization that would gain a large influence on world politics and the global economy as a result of their discoveries. After discovering human immortality, much of mankind opted to become immortal despite the side effect of losing their reproductive functions. Led by APE after the sudden emergence of the Klaxosaurs, the remnants of human civilization relocated to Plantations and the Franxx units were later created to combat the Klaxosaur threat.