We integrated transcriptomic, proteomic, and untargeted metabolomic profiling of placentas from PE patients and normotensive controls, followed by validation in an independent clinical cohort. Mechanistic roles were interrogated using hypoxia-treated HTR-8/SVneo trophoblasts and an L-NAME–induced PE-like mouse model. Autophagy dynamics were assessed using dual-fluorescent autophagic flux reporters, transmission electron microscopy, and molecular markers.