Uranium (U) contamination of the environment due to nuclear processing activities causes significant economic and health problems due to its presence in terrestrial and aquatic ecosystems. Understanding the mobility of U at the microscale is critical for predicting its macroscale fate and for optimizing remediation strategies. Mathematical modeling can provide a non-intrusive and low-cost alternative to difficult and expensive laboratory and field experiments. In this study, we developed a 2-dimentionsal mathematical model to monitor U mobility inside Shewanella oneidensis MR-1 biofilms. Biofilms are comprised of a matrix of cells and abundant extracellular polymeric substances (EPS), both loosely-associated and bound EPS. Specifically, our model focused on (1) the contribution of cells and EPS to immobilize U, (2) the effect of U on cellular metabolism and EPS production, and (3) the relative role of adsorption and reduction on overall U immobilization. The model was developed and solved using COMSOL Multiphysics software. Our model demonstrated that U preferentially binds to specific locations within the biofilm, which U detrimentally affects cellular metabolism, and that loosely associated and bound EPS interact differently with U.