Abstract The water-energy-food-ecosystems (WEFE) Nexus has gained recognition as an innovative approach for analysing the interconnectedness of global resource systems and achieving sustainability goals. In the Mediterranean, where water scarcity, climate change, and ecosystem degradation pose significant challenges, implementing an integrated WEFE Nexus approach is crucial. We conducted a comprehensive review of scientific literature through the lenses of Nexus ‘ideas’, ‘relationship’ and ‘practices’. A total of 142 research articles were selected and characterized in terms of WEFE interlinkages being investigated, explored topics, methods and scales of analysis, and contexts of operationalization. We found that water-energy interdependences dominate WEFE Nexus research in the Mediterranean, driven by the large presence of energy-intensive water abstraction and distribution systems to meet drinking and irrigation water demands. At the same time, the expansion of the Nexus approach to additional components is only partial, mostly focusing on assessing impacts on the physical environment and climate, without capturing feedback dynamics. Geographically, Nexus research in the Mediterranean is primarily conducted in isolated case studies, with few large scale assessments developed at the entire Mediterranean scale, and with some countries not yet represented, in particular the Western Balkans. Although WEFE Nexus research in the Mediterranean is recognizing the importance of transdisciplinarity moving beyond biophysical assessments to encompass societal and governance dynamics, further research is needed on understanding the economic implications of WEFE Nexus interactions. To advance Nexus implementation in the region, sustainable technology, and natural resources management, which are key fields of WEFE Nexus research operationalization, would benefit from harmonization in their design objectives. This would enable a more comprehensive and coherent approach towards achieving water, food, and energy security while preserving the environment in the Mediterranean region.