Karst environments, especially in Mediterranean area, are highly vulnerable to natural and anthropogenic contamination. This study presents a comprehensive hydrogeochemical assesment of surface water and groundwater across a 2300 km2 catchment area spanning Southern Dalmatia (Croatia) and Western Herzegovina (Bosnia and Herzegovina).For the first time in the study area, data were collected over six years integrating ion analysis, sulphur isotope (δ34S) composition, and physical-chemical analysis of water from 30 locations. The research identified four hydrogeochemical facies (carbonate, sulphate, mixed carbonate/sulphate and chloride), influenced by seawater intrusion, carbonate dissolution, evaporite presence, and human activities.Elevated sulphate levels, often exceeding 250 mg/L, were a main focus of the study due to their potential risks to drinking water quality. The study developed a conceptual model to explain the distribution of sulphates, underscoring the importance of evaporite diapirism and δ34S analysis in tracing sulphate origins. These findings contribute to an improved understanding of karst systems and offer essential data for groundwater protection and legislative measures in the Mediterranean region.