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Like all other Mediterranean countries, Tunisia provides multiple examples of groundwater degradation due to its overexploitation. This is especially the case in the Zeramdine-Mandia-Jebeniana region (central east Tunisia), where recent measurements revealed an important piezometric drop in the Miocene aquifers. Through hydrodynamic and hydrochemical analysis, we studied the influence of the head decrease on groundwater flow and quality. The spatial and temporal analysis of the piezometry identified two totally independent compartments. This was confirmed by the hydrogeochemical and multivariate statistical analysis. The Miocene aquifer system was divided into two water groups: (I) the Zeramdine-Beni Hassen aquifer which is characterized by freshwater, Na-Ca-Cl-SO4 facies, and salinity increase from west to east that is coinciding with the principal water flow direction; and (2) the Mandia-Ksour Essef aquifer, which is defined throughout by high and heterogeneous salinity and Na-Cl facies.