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Radon (Rn) is a natural and toxic radioactive gas that accumulates indoors, mainly in low-ventilated underground floors and basements. Several factors make prediction of indoor Rn exposure in enclosed spaces challenging. In this study, we investigated the influence of soil, geology, topography, atmospheric variables, radiation, urbanization, community economic well-being, and monthly and yearly variations on indoor Rn concentrations. We analyzed 7,515 monthly indoor Rn measurements in 623 zip codes from two U.S. States (Michigan and Minnesota) during 2005–2018 using a random forest model. Using Shapley Additive exPlanations (SHAP) values we investigated the contribution of each factor using variable importance and partial dependence plots. Factors that predict indoor Rn differed between states, with topographical, geological and soil composition being most influential. Cross-validated Pearson correlation between predictions and measurements was 0.68 (RMSE = 47.8 Bq/m3) in Minnesota, and 0.67 (RMSE = 52.5 Bq/m3) in Michigan. Our results underline the importance of soil structure for radon exposure, presumably due to strapped Rn in soil. The differences across states also suggest that Rn studies performing model development should consider geographical variables, along with other factors. As indoor Rn levels are multifactorial, an understanding of the factors that influence its emanation and build up indoors will help better assess spatial and temporal variations, which will be useful to improve prevention and mitigation control strategies. Implications: Radon exposure has become a year-round problem as people spend most of their time indoors. In North America, radon exposure is increasing over time and awareness related to its health effects remains low in the general population. Several factors make prediction of indoor radon exposure in enclosed spaces challenging. In this study, we used random forest to investigate the influence of factors on indoor radon in the Midwest United States. We found that topography, geology, and soil composition were the most influential factors on indoor radon levels. These results will help better assess spatial and temporal variations, which will further help better prevention and mitigation control strategies. [ABSTRACT FROM AUTHOR]