Maternal exposure to persistent organic pollutants (POPs) has been linked with adverse pregnancy and birth outcomes, yet the underlying biological pathways involved remain poorly characterized. In this study, we examined associations between POP concentrations in maternal plasma and cord blood and metabolomic and lipidomic profiles of pregnant women and their newborns and further assessed relationships with neonatal birth weight. A total of 257 mother–infant dyads were included. Concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs) were quantified using gas chromatography coupled with atmospheric pressure tandem mass spectrometry (GC–MS/MS). Metabolomic profiling was performed using gas chromatography coupled with quadrupole time-of-flight mass spectrometry (GC–QTOFMS) and ultrahigh-performance liquid chromatography–QTOFMS (UHPLC–QTOFMS). In maternal plasma, POP exposure was predominantly associated with variations in free fatty acids, phospholipids, and triacylglycerols. The strongest associations were observed for p,p′-DDE and trans-nonachlordane, with p,p′-DDE also positively associated with the gut microbiota-derived metabolite indole-3-propionic acid. Several PCB congeners (74, 163, 170, and 180) showed pronounced associations with individual lipid species, particularly those containing polyunsaturated or monounsaturated fatty acyl chains. Although no significant associations were observed between POP exposure and neonatal birth weight, POP exposure was significantly associated with the cord blood metabolome, characterized by predominantly inverse associations with polyunsaturated fatty acid-containing lipids. Overall, these findings provide insights into metabolic pathways potentially linking maternal POP exposure with alterations in lipid and metabolomic profiles during pregnancy and early life.