In South Transdanubia (Hungary), the remarkable geothermal and hydrocarbon resources in the Drava Basin and the hypogene caves at the margin of outcropping carbonate hills were usually investigated separately and their interactions were hitherto neglected. The aim of this study is to give all these groundwater-related resources and phenomena a common framework applying the concept of regional hydraulic continuity, and to complete the regional (i.e., basin-scale) hydraulic assessment of the area based on preproduction archival measured data. Pressure-elevation profiles, tomographic fluid-potential maps and hydraulic cross-sections were constructed to determine the vertical and horizontal fluid-flow conditions. As a result, two kinds of fluid flow systems could be identified. Within the gravitational flow systems, horizontal flow conditions are dominant and the regional flow direction tends toward the S–SE. In deeper basin regions, an overpressured flow system is prevalent, where fluids are driven laterally from the deeper sub-basins towards their margins. Based on the regional-scale evaluation of fluid flow systems, conclusions could be drawn regarding the geothermal and hydrocarbon potential of the area. Additionally, local-scale phenomena could be explained, particularly in the southern foreland of the Villány Hills. Cave formation cannot be related to the present-day flow systems here. In the Harkány area, groundwater chemistry could be explained by fluid contribution from the Drava Basin. A comparison with the marginal Buda Thermal Karst area allows for generalized conclusions regarding the connections between marginal karst reservoirs and the Pannonian Basin.