A modelling study on a multi-layered confined/unconfined alluvial aquifer system was performed to quantify surface water/groundwater interactions. The calibrated groundwater flow model was used to forecast climate change impacts by implementing the results of a downscaled A1B model ensemble for the Po river valley. The modelled area is located in the north-western portion of the Ferrara Province (Northern Italy), along the eastern bank of the Po river. The modelling procedure started with a large scale steady state model followed by a transient flow model for the central portion of the domain, where a telescopic mesh refinement was applied. The calibration performance of both models was satisfactory, in both drought and flooding conditions. Subsequently, forecasted rainfall, evapotranspiration and Po river stage at 2050, were implemented in the calibrated large scale groundwater flow model and their uncertainties discussed. Three scenarios were run on the large scale model: the first simulating mean hydrological conditions and the other two simulating one standard deviation above and below the mean hydrological conditions. The forecasted variations in groundwater/Po river fluxes are relevant, with a general increase of groundwater levels due to local conditions, although there are large uncertainties in the predicted variables.