The Mediterranean Basin, already a water-scarcity hotspot, faces intensifying droughts and warming that strain the water–energy–food–ecosystems (WEFE) nexus. Climate impacts cascade across sectors, while siloed responses risk maladaptation. Nexus-based solutions—centred on water—can foster synergies and reduce trade-offs, with nature-based, socially inclusive, and clean energy strategies offering transformative potential. Yet governance, cooperation, and data gaps persist; closing these is vital to operationalize the nexus and advance regional sustainability.