In this study, critical extreme events affecting salt intrusion are investigated using an unstructured 3D hydrodynamic model applied to a coastal system comprising the Po River Delta and the nearby Emilia-Romagna coast located in the Northern Adriatic Sea (Italy). River–sea systems respond to severe floods and droughts through two mechanisms: enhanced saltwater intrusion (SWI) under conditions of reduced freshwater availability, and the formation of buoyant freshwater plumes (FWPs) during flood events, which modify coastal stratification and transport processes. During the 2022 drought, along-river salinity profiles confirmed that the model captured the vertical structure and inland propagation of the salt wedge, although the maximum saltwater intrusion was locally underestimated by a few kilometers. During drought conditions, reduced river discharge led to enhanced SWI, with saline water propagating several kilometers inland on the main distributary branches, together with a strong vertical stratification and persistent bottom salinity; while flood conditions generate short but intense freshwater pulses that propagate offshore over several kilometers, generating multiple coalescing river plumes, altering coastal stratification and mixing patterns. These contrasting responses highlight the sensitivity of river–sea systems to extreme forcing and their implications for water resources, ecosystem dynamics, and coastal processes. This work provides an integrated assessment of SWI and FWP dynamics under real extreme events, demonstrating how tools like process-based models can inform the prediction and management of hydroclimatic extremes in transitional environments.