Water, energy, food, and ecosystems (WEFE) are interconnected, comprising a coherent system (nexus) dominated by complexity and modulated by climatic and socio-economic drivers. Resource constraints, and their interconnectedness could hamper economic development, including optimal trade, market and policy solutions. NEXOGENESIS offers a coherent WEFE nexus framework for the assessment of potential impact pathways of implementing new policy objectives (WFD, RED, CAP, SDGs, Paris Agreement) in the nexus, including: (i) biophysical and socio-economic modelling; (ii) stakeholder engagement together with; (iii) validation of NEXOGENESIS outputs and; (iv) use of the latest artificial intelligence techniques.