Abstract: Endometriosis (EMs) is a common estrogen-dependent disease frequently accompanied by inflammatory responses and tissue fibrosis. Recent multi-omics and mechanistic studies have demonstrated that systemic lipid metabolic reprogramming plays a critical role in the initiation, maintenance, and progression of EMs. Through a systematic review of the literature, this paper identifies the following two pathways linking lipid metabolism to EMs: (1) Pathological effects of lipid metabolism-related substances: an imbalance in the free fatty acid profile, accumulation of cholesterol and oxidized cholesterol, and abnormal activation of signaling pathways such as Toll-like receptor 4 and peroxisome proliferator-activated receptors by adipokines (leptin, adiponectin, and resistin) promote the proliferation, angiogenesis, and tissue fibrosis of ectopic endometrial cells; (2) Lipid metabolism-immune interaction network: lipid influx induces metabolic reprogramming of immune cells, manifesting as macrophage pro-inflammatory polarization/foam cell formation, decreased natural killer cell cytotoxicity, and an imbalance between T helper 17 cells and regulatory T cells, which in turn leads to failure of immune clearance, persistent inflammation, and lesion expansion. In addition, this paper reviews therapeutic strategies targeting lipid metabolism, including dietary interventions (optimizing the ω-3/ω-6 polyunsaturated fatty acid ratio), statins, and agents targeting adipokines or immunomodulators, with the aim of providing new therapeutic avenues for the precise prevention and treatment of EMs.