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Climate change and rapid population growth threaten food, water and ecosystem security in the Mediterranean region. The Water-Ecosystems-Food (WEF) Nexus concept builds on the complex (spatial, temporal, institutional, jurisdictional) interdependencies between water, ecosystems and food security as it presents an integrated approach to resource management. The overarching objective of SIGMA-Nexus is to develop climate resilience in the Mediterranean region by proposing sustainability pathways within the WEF Nexus framework. SIGMA-Nexus will analyse the socio-economic and technical characteristics of several case study sites in Egypt and Greece to develop the WEF Nexus for different hydrological, agricultural and environmental settings in the Mediterranean region. This will provide a basis for SIGMA-Nexus’ targeted interdisciplinary efforts to address synergies and conflicts observed in the three facets of the WEF Nexus, to draw lessons from previous successes or failures, to develop frameworks that advocate the efficient, integrated use and management of land and water, and to break disciplinary silos. SIGMA-Nexus aims to accelerate knowledge diffusion and support decision-making that can minimize conflicts and maximize synergies of cross-institutional and sectoral management of water and land resources through participatory multi-stakeholder engagement activities. The proposed project will design and prioritize Nexus practices that encourage scalability and appraise interventions that balance ecological, socio-economic and natural resource aspects. Finally, SIGMA-Nexus will develop and promote a WEcoF digital innovation portal that will not only promote co-design of Nexus initiatives but also act as a capacity-building tool.