Metabolic dysfunction-associated steatosis liver disease (MASLD) is the most common form of chronic liver disorder and affects millions of individuals worldwide. Exposure to environmental factors such as perfluoroalkyl substances (PFAS) has been shown to contribute to MASLD development and progression. PFAS are a group of chemicals that are pervasive in the environment due to their use in commercial and industrial products and have been shown to target the liver and induce metabolic perturbations that can lead to hepatotoxicity, liver cell injury, and increased risk to MASLD, but the underlying mechanisms remain incompletely understood. We hypothesize that PFAS induce cell- type specific transcriptomic and epigenetic alterations to perturb pathways and networks involved in MASLD. In this study, C57BL/6J male mice were exposed orally to a legacy PFAS chemical, perfluorooctanoic acid (PFOA), for four weeks and monitored for metabolic phenotypes followed by the analysis of the liver gene expression and chromatin accessibility at a single cell resolution. We found that PFOA significantly increases liver weight and liver injury biomarkers. Our single cell multiomics analysis of six cell types and four zone-specific hepatocytes revealed that midcentral and portal hepatocytes showed more significant alterations in both gene expression and chromatin accessibility after PFOA treatment. Genes affected are involved in PPAR⍺ and PPARγ signaling, metabolic pathways (cholesterol, fatty acids, amino acids, glucose metabolism), complement and coagulation, TNF⍺ signaling, carcinogenic pathways, and xenobiotic metabolism. Altered open chromatic peaks were enriched for PPAR⍺ and PPARγ binding sites, and our transcription factor enrichment analysis further identified additional transcription factors (e.g., LXR, RXR, ESR1, FOXO1, JUN, etc) as potential regulators of PFOA-affected genes. Additional non-transcription factor gene network modeling revealed network key drivers that may play a role in the urea cycle (Cps1 and Asl) and fibrinolysis, immunity, and wound healing (Plg, Serpinf2, and Vtn). Our single cell multiomics study sheds light on the cell-type specific transcriptomic and epigenetic perturbations induced by PFOA, particularly in midcentral and portal hepatocytes, that affect diverse metabolic, immune, and tissue injury pathways through various transcriptional and network regulators involved in MASLD. Our findings provide insights into the molecular underpinnings of PFAS that can guide future mitigation strategies against PFAS-induced liver diseases such as MASLD.