The unconformity-related uranium deposits in the eastern part of the Athabasca basin (Saskatchewan, Canada) are described as structurally-controlled due to their spatial relationship to reactivated basement fault system. The deposits are found at the intersection between two or more fault arrays and vary in orientation from NNE-SSW to E-W direction at a short distance. It is widely accepted that these faults are reactivated under NW-SE pure compressional regime at regional scale. However, the reactivation mechanism and variation of reactivated fault arrays from one mineralization site to another remain unclear. Nevertheless, successive remobilization and reprecipitation processes, associated to different regional tectonic events suggest a role of fault-valve of large and deeply-rooted faults, suggesting a second potential reactivation mechanism. In this study, the tectonic stress (brittle deformation) and injection of overpressured fluid (fault-valve behavior) are discussed as two possible mechanisms of fault reactivation at mineralization sites. Two types of 3-D hydromechanical modeling have been conducted to assess the two mechanisms. In the first modeling type, a series of simplified models of two intersecting faults are run to evaluate the effects of overpressured fluid injection and approaching angle on fault reactivation. In the second modeling type, a well-constrained 3-D model of a real-case example (e.g., the Cigar Lake area) is used to estimate the effect of different angles of compressional stress on reactivation of different fault sets, using a constant horizontal convergence rate. The results of the first modeling show that the reactivated faults could vary in orientation due to overpressured fluid, depending on the relative angle between faults, and on the applied tectonic regime. In the second model, the reactivation of a specific fault set from one mineralization setting to another depends on the direction at which the convergent rate is applied. The results suggest that at a local scale, the change in reactivated fault sets at mineralizing locations depend more likely on an episodic injection of overpressured fluid than a change of convergent direction within a local area.