This study investigates the thermal performance of closed-loop advanced geothermal systems under the influence of groundwater flow in deep sedimentary formations. By integrating advective heat transport into a 3D numerical model, we evaluate the combined effects of groundwater flow in deep sedimentary aquifers and geothermal heat transport and extraction using U-shaped closed-loop geothermal wells. The model is developed to simulate heat-transfer dynamics, incorporating well design with realistic casing and cement layers, layered geology with associated petrophysical uncertainties, and varying operational conditions. As study area, we selected the Midyan basin in Saudi Arabia, characterized by thick sedimentary formations and an elevated geothermal gradient. The results show that the advective heat transfer, induced by groundwater flow, significantly enhances system efficiency. Improvement in thermal power output increases by up to 27% over a 40-year operational period compared to conduction-only scenarios, particularly if groundwater flow is perpendicular to the lateral section of the wellbore. Sensitivity analysis reveals that geothermal gradient and reservoir depth are the most impactful geological parameters. Operational parameters such as injection rates (10—100 kg/s) and injection temperatures (25—45 °C) can be adjusted to further optimize the system performance, with 30 kg/s identified as the optimal injection rate that balances energy extraction and parasitic pumping losses. Well-design parameters, including diameters (0.114–0.245 m) and lateral length (0.5–3 km), also play a critical role, with longer lateral sections and larger diameters increasing the overall power output. These findings show the potential of U-shaped closed-loop advanced geothermal systems in sedimentary basins with dynamic groundwater flow and provide insights for optimizing geothermal energy systems in similar geological settings.