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A successful utilization of deep geothermal resources requires accurate predictions about the distribution of reservoir temperature as well as of the hydraulic processes exerting a direct influence on the productivity of geothermal reservoirs. The aim of this study was to investigate and quantify the influence that regional thermo-hydraulic processes have on the geothermal configuration of potential reservoirs in the German Federal State of Hesse. Specifically, we have addressed the question of how the regional thermal and hydraulic configuration influence the local hydro-thermal reservoir conditions. Therefore, a 3D structural model of Hesse was used as a basis for purely hydraulic, purely thermal and coupled 3D thermo-hydraulic simulations of the deep fluid flow and heat transport. As a result of our numerical simulations, Hesse can be differentiated into sub-areas differing in terms of the dominating heat transport process. In a final attempt to quantify the robustness and reliability of the modelling results, the modelling outcomes were analyzed by comparing them to available subsurface temperature, hydraulic and hydrochemical data.