This study presents integrated isotope-geochemical data on groundwater from the southern part of Western Siberia to identify the factors of uranium mobilization. Groundwater within the multi-aged, complex rock aquifer system is predominantly of HCO₃-Mg-Ca type, whereas waters hosted in granitoid units (the Priobsky and Barlak complexes) exhibit SO₄-HCO₃-Na-Mg-Ca characteristics. Measured ²²²Rn activity ranges from 1 to 1161 Bq/L. This study systematically evaluated the disequilibrium state of uranium isotopes (²³⁴U/²³⁸U) across contrasting hydrogeological settings: granitoid massifs, contact zones, and sedimentary complexes of different ages. Maximum ²³⁴U excess occurs in granitoid-hosted groundwater, confirming the Priobsky and Barlak complexes as the primary uranium sources in the region. Stable isotope signatures (δ²H, δ¹⁸O) confirm the meteoric origin of the groundwater, with recharge of the Paleozoic bedrock aquifer complex being unaffected by short-term seasonal variations. Thermodynamic modeling classifies all studied waters as a single geochemical type: siliceous-Na (Ca-Mg-K). Elevated uranium concentrations are directly linked to granitoid lithologies hosting accessory minerals (e.g., uraninite, monazite, zircon, bastn asite) that accumulate uranium, thorium, and rare earth elements. Radionuclides are released into groundwater as a result of mineral weathering. Under oxidizing conditions, uranium remains mobile in the form of uranyl ion (UO²2+₁₈), whereas thorium is immobilized via adsorption onto mineral surfaces or precipitation. Subsequent uranium precipitation at redox boundaries may contribute to the formation of paleovalley-type infiltration uranium deposits. These findings advance the understanding of uranium mobilization pathways and support targeted assessments of groundwater safety and mineral potential in crystalline terrains.