Seismic prospecting has been accepted as one of the most widely available methods for exploring sandstone-hosted uranium deposits (SUDs). However, conventional seismic interpretation faces a challenge in the identification and characterization of a uranium reservoir’s complexity. How to characterize in detail a uranium reservoir’s physical complexity and effectively improve uranium reservoir prediction accuracy remain unresolved problems. To address this, we develop a novel combination of petrophysical modeling and prestack simultaneous inversion to understand in detail the physical properties of uranium-bearing reservoirs and efficiently predict favorable SUD sites. First, we develop a workflow of rock-physics modeling for SUD logs using the Xu-White method to calculate the modulus of elasticity of the grain matrix; subsequently, we extend the Walton model for the modulus prediction of the dry rocks and the Gassmann equation for one of the saturated rocks after a massive calculation test; and then, we predict the S-wave data used for the following inversion. Second, we execute a prestack simultaneous inversion to obtain the petrophysical parameters (e.g., P-impedance, density [[Formula: see text]], shear modulus [[Formula: see text]], Lamé coefficient [[Formula: see text]], and Young’s modulus) that can provide insights into the physical properties of a uranium metallogenic environment. Accordingly, we discover that sites bearing uranium mineralization strongly correspond to areas with low elastic-parameter values (especially [Formula: see text] and [Formula: see text]), whereas nonuranium anomalies occur in high-value sites. This indicates that weakened elastic characteristics are caused by the enhancement of the total organic content and total clay mineral volumes of the uranium-bearing layers. In summary, the developed combination approach can yield an effective and accurate characterization of the geologic properties of uranium-bearing formations, and it can provide prediction factors (e.g., parameters related to the shear modulus) for uranium mineralization.