Study region: " Jeffara de Medenine " aquifer system in southeastern Tunisia. Study focus: This study investigates the role of fault structures in the distribution of hydro-geochemical facies and groundwater compartmentalization for the aquifer system. New hydrological insights for the region: The proposed methodology, including seismic structural study, hierarchical cluster analysis and geostatistical methods, allowed an efficient multi-element characterization of the spatial patterns of the structural elements in the aquifers and of the hydrogeological parameters used in a spatial cross-correlation to explore the dependence of the geochemical properties in each " geochemical population " on the hosting structural compartment to delineate the different geochemical compartments. The tectonic studies showed that the lateral extent of the aquifers is controlled by normal faults. The multivariate statistical analysis revealed a strong spatial coherence between hydrogeochemical facies clustering and the reservoir compartments at both large and small scales. The kriged maps of major-ion concentrations and of total dissolved solids in the aquifers were then analyzed and compared with the reservoir facies distribution for each compartment , the geometric characteristics of the aquifer, and the piezometric level trends. This allowed to characterize the hydraulic behavior of the Medenine fault and to understand the underlying physical and chemical processes having led to the spatial distribution of the geochemical properties, and thus, the hydrogeochemical functioning of the aquifers.