This study investigates the association between prenatal exposure to endocrine-disrupting chemical (EDC) mixtures and the risk of metabolic syndrome (MetS) in children. The research is based on data from the Human Early Life Exposome (HELIX) cohort, which includes mother-child pairs from France, Greece, Lithuania, Norway, Spain, and the UK. The study assessed prenatal exposure to nine metals, three organochlorine pesticides, five polychlorinated biphenyls, two polybrominated diphenyl ethers, five perfluoroalkyl substances, ten phthalate metabolites, three phenols, four parabens, and four organophosphate pesticide metabolites. The main outcome measure was a composite MetS risk score, which included waist circumference, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and insulin levels. Child levels of 44 urinary metabolites, 177 serum metabolites, and 35 plasma proteins were also quantified. The results showed that prenatal exposure to EDC mixtures, particularly metals, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances, was associated with an increased MetS risk score in childhood. In contrast, high-molecular-weight phthalate mixtures and low-molecular-weight phthalate mixtures were associated with a decreased MetS risk score. Most EDC mixtures were associated with elevated proinflammatory proteins, amino acids, and altered glycerophospholipids, which in turn were linked to increased MetS scores. The study suggests that prenatal exposure to widespread EDC mixtures may contribute to adverse metabolic health in children and highlights the need for early-life prevention and intervention strategies to address the rising trends in MetS across the life course.This study investigates the association between prenatal exposure to endocrine-disrupting chemical (EDC) mixtures and the risk of metabolic syndrome (MetS) in children. The research is based on data from the Human Early Life Exposome (HELIX) cohort, which includes mother-child pairs from France, Greece, Lithuania, Norway, Spain, and the UK. The study assessed prenatal exposure to nine metals, three organochlorine pesticides, five polychlorinated biphenyls, two polybrominated diphenyl ethers, five perfluoroalkyl substances, ten phthalate metabolites, three phenols, four parabens, and four organophosphate pesticide metabolites. The main outcome measure was a composite MetS risk score, which included waist circumference, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and insulin levels. Child levels of 44 urinary metabolites, 177 serum metabolites, and 35 plasma proteins were also quantified. The results showed that prenatal exposure to EDC mixtures, particularly metals, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances, was associated with an increased MetS risk score in childhood. In contrast, high-molecular-weight phthalate mixtures and low-molecular-weight phthalate mixtures were associated with a decreased MetS risk score. Most EDC mixtures were associated with elevated proinflammatory proteins, amino acids, and altered glycerophospholipids, which in turn were linked to increased MetS scores. The study suggests that prenatal exposure to widespread EDC mixtures may contribute to adverse metabolic health in children and highlights the need for early-life prevention and intervention strategies to address the rising trends in MetS across the life course.