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Land, food, energy, water and climate are linked and interconnected into a Nexus, characterized by complexity and feedbacks. An integrated management of the Nexus is critical to understand conflicts/synergies and secure efficient and sustainable use of resources, especially under climate change. The Nexus perspective is applied to Sardinia, as regional case study, to better understand and improve integrated resource management and relevant policy initiatives. Vulnerability of Sardinia Nexus is assessed under several climate projections by articulated balances of resources (water, energy) availability and sustainable development goals, at regional and sub-regional scales, accounting for demands and conflicts among key economic sectors (agriculture, hydro-power, tourism).