Climate change and growing populations are placing additional pressure on the availability of food, energy and water in the Mediterranean, accompanied by an increased environmental footprint. The Water, Energy, Food, Ecosystems Nexus (Nexus) approach is key to ensuring resilient, circular and green economies and to achieve the Sustainable Development Goals, and Nexus demonstrators are already showing its transformative potential for the Region. However, there is a long way ahead before the Nexus approach is mainstreamed and applied at large in policies and practices. To ramp up uptake, a robust mechanism is needed to support mobilization of a range of stakeholders across countries, sharing their expectations, experiences and knowledge, and providing evidence of benefits to policy makers, investors, businesses, practitioners and society at large. Heeding the call for action at the WEFE Nexus Science Advances Conference, WEFE4MED will gather scientists, practitioners, policymakers, investors, local authorities, the media and other stakeholders in a Mediterranean WEFE Nexus Community of Practice (NCoP) to provide convincing practical and scientific evidence of the Nexus benefits as a basis for decision-making in integrated natural resources management. WEFE4MED will achieve this by identifying, federating and promoting examples of best practice around the Mediterranean, including demonstrator projects, having Nexus at their core. It will foster long-lasting cooperation between actors as well as demonstrator projects to replicate and upscale them in other countries, and to disseminate their achievements, including as part of a science-based advocacy effort aimed at policy-makers and investors. In doing so, WEFE4MED will establish an open digital Nexus Knowledge Hub, will twin flagship demos and promote mutual learning among knowledge holders while promoting external funding opportunities. Through a structured participatory process, WEFE4MED will design, establish and operate a functional dialogue and cooperation platform that will persist well beyond the project lifespan, due to the commitment to Nexus objectives of the project partners and NCoP members.