In the basement areas of the southern Pannonian Basin, Central Europe (Tisia Composite Terrane, Hungary), Variscan blocks are essential components. The existing paleogeographic reconstructions, however, are often unclear and contradictory. This paper attempts to give a contribution for paleogeographic correlation of the Tisia using paleohydrological features (e.g., vein mineralization types, inclusion fluid composition and origin) of the Pennsylvanian continental succession and neighboring crystalline complexes. Vein-type mineralization in the studied samples dominantly forms blocky morphological types with inclusion-rich quartz and carbonate crystals. The evolution of hydrothermal mineralization and host rock alteration in the study area comprises three major stages. The first one is characterized by chloritization, epidotization, and sericitization of metamorphic rocks together with subsequent formation of Ca-Al-silicate and quartz-sulfide veins (clinopyroxene-dominant and epidote-dominant mineralization). The related fluid inclusion record consists of high-temperature and low-salinity aqueous inclusions, corresponding to a reduced retrograde-metamorphic fluid phase during the Late Westphalian (~310 Ma). The next mineralization stage can be related to a generally oxidized alkaline fluid phase with a cross-formational character (hematite-rich alkali feldspar-dominant and quartz-dolomite veins). High-salinity primary aqueous inclusions probably were originated from the Upper Permian playa fluids of the region. The parent fluid of the third event (ankerite-hosted inclusions) was derived from a more reductive and low-salinity environment and can represent a post-Variscan fluid system. Fluid evolution data presented in this paper support that the W Tisia (Mecsek–Villány area) belonged to the Central European Variscan belt close to the Bohemian Massif up to the Early Alpine orogenic phases. Its original position is presumably to the northeast from the Bohemian Massif at the Late Paleozoic, north to the Moravo-Silesian Zone. The presented paleofluid evolution refines previous models of the paleogeographic position of the Tisia and puts constraints on the evolution of the Variscan Europe.