Deltaic coastal areas are constituted by a patchwork of brackish lagoons and freshwater bodies; these coastal wetland-aquifer systems are fragile ecosystems that usually respond quickly to climate changes. To understand the hydrological processes occurring within the lagoons and the groundwater system of the Po River Delta (Italy), the contribution of both evaporation and anthropogenic factors on groundwater salinization was assessed. A time series (2002–2015) of monthly average climatic data and a temperature-salinity dataset were used in three adjacent saline-brackish lagoons with the aim to identify the actual evaporation patterns and predict future trends using artificial neural networks (ANN). Moreover, the use of groundwater and surface water equivalent freshwater heads, along with the geological architecture, allowed linking the fluctuation of lagoon salinities with the degree of hydraulic connection between wetland and aquifer system. Results show that the less a lagoon is hydraulically connected with the aquifer, the higher is the salinity peak that could be reached at the end of the summer period. ANN forecasts highlight that in the near future this behaviour would be the rule rather than the exception. The increase in salinity of surface waters could be of serious concern, especially for aquaculture, sensitive to sharp salinity increases.