Despite the fact that numerous human epidemiology and animal model studies have implicated a pathogenic role of developmental exposure to endocrine disrupting chemicals (EDCs) in promoting obesity, type 2 diabetes, and cardiovascular diseases, the underlying molecular mechanisms remain poorly understood. We have recently conducted a systems biology study in mice to comprehensively examine the multi-tissue transcriptome, epigenome, and gut microbiome alterations altered by developmental EDC exposure. As a result, we identified key genes, pathways, and tissue-specific regulatory networks that are perturbed in endocrine and metabolic tissues (hypothalamus, liver, and adipose tissues) and associated with metabolic dysfunctions. However, all previous molecular studies of EDCs, including ours, examined bulk tissues that represent mixtures of heterogeneous cell populations, thereby missing the opportunity to pinpoint the most sensitive and pathogenic cell types and cell-specific molecular pathways. Building on our recent success in implementing high-throughput single cell sequencing technology Drop-seq, here we propose to understand the multi-tissue, multi-cellular molecular perturbations induced by in utero exposure in mice to two common EDCs, namely, the model chemical Bisphenol A (BPA) and its much less well-understood substitute Bisphenol S (BPS) at single cell resolution. We will focus on the liver, adipose, and hypothalamic tissues due to their pivotal roles in obesity and metabolic dysfunction. Using Drop-seq, we will identify the most sensitive cell types and molecular pathways in individual cell types in each metabolic tissue that are affected by developmental exposure to BPA and BPS, and subsequently test the roles of the molecular changes in metabolic dysregulation. Our proposed pilot study will offer the first comprehensive map of the in vivo molecular activities of common EDCs in individual cell types of key metabolic tissues and will reveal key mechanistic commonalities and differences between BPA and BPS to facilitate precision medicine. The findings will help direct future therapeutic strategies to counteract EDC-induced cardiometabolic disorders.