The severe drought that affected large areas of Europe in Spring and Summer 2022 hit the Po valley (northern Italy) with an intense water scarcity crisis. Productive activities, particularly agriculture, suffered the consequences of water shortage, and the coastal regions of the Po Delta underwent extensive saltwater intrusion. By relying on observed discharge records and on precipitation data from reanalysis and climate models, we analyse the 2022 event in the framework of the recent past statistics and in future scenarios. Alongside with a projection of future rainfall regimes on the Po River basin in two climate change scenarios, our analysis shows that persistent negative rainfall anomalies like the ones that characterised the 2022 event, though unlikely to become a typical feature of future climate, could remarkably increase their frequency, particularly in a severe climate change condition. Moreover, their impacts will be magnified by rising temperatures and, in coastal areas, by rising sea level, enhancing the salinisation of agricultural lands and altering the dynamics of transitional ecosystems. While providing a first quantitative assessment of an event that struck a strategic productive and environmental region of the Italian territory, this brief communication points out the importance of a multi-disciplinary, basin-scale approach to climate change adaptation.