This study aims to investigate the combined effects of per- and polyfluoroalkyl substances (PFAS) on allostatic load, an index of chronic stress that is linked to several chronic diseases, including cardiovascular disease and cancer. Using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2014, this study examines the relationship between six PFAS variables (PFDE, PFNA, PFOS, PFUA, PFOA, and PFHS) and allostatic load using Bayesian Kernel Machine Regression (BKMR) analysis. The study also investigates the impact of individual and combined PFAS exposure on allostatic load using various exposure-response relationships, such as univariate, bivariate, or multivariate models. The analysis reveals that the combined exposure to PFDE, PFNA, and PFUA had the most significant positive trend with allostatic load when it was modeled as a binary variable, while PFDE, PFOS, and PFNA had the most significant positive trend with allostatic load when modeled as a continuous variable. These findings provide valuable insight into the consequences of cumulative exposure to multiple PFAS on allostatic load, which can help public health practitioners identify the dangers associated with potential combined exposure to select PFAS of interest. In summary, this study highlights the critical role of PFAS exposure in chronic stress-related diseases and emphasizes the need for effective strategies to minimize exposure to these chemicals to reduce the risk of chronic diseases. It underscores the importance of considering the combined effects of PFAS when assessing their impact on human health and offers valuable information for policymakers and regulators to develop strategies to protect public health.