The interdependence of crucial resources and the imperative for ensuring sustainability through integrated management approaches is underscored by the Water-Energy-Food (WEF) Nexus. The current study focuses on Alabama, Arkansas, Louisiana, Mississippi, and Tennessee in the Deep South USA to analyze the trade-offs and synergies in WEF Nexus. We propose an Integrated WEF Sustainability Index (IWSI) to provide a quantitative assessment of sustainability across these states. The IWSI is constructed by integrating standardized indicators across the water, energy, and food sectors, with weights derived from inter-sectoral economic interactions, to capture both trade-offs and synergies in a single composite score to provide an aggregated sustainability assessment. USA has an IWSI value of 1.62. Tennessee has an IWSI value of 2.34, characterized by efficient water utilization, substantial contributions from renewable sources, and robust agricultural productivity. Conversely, Louisiana and Arkansas encounter notable sustainability challenges, respectively, primarily attributable to low energy and water efficiency, reliance on fossil fuels, high emissions, and large water footprints. Arkansas demonstrates a significant water footprint in agriculture, well above the national average, highlighting its heavy reliance on irrigation. There is variation in hydropower conditions across states, with Tennessee leading in renewable energy use. The study underscores regional disparities in sustainability and emphasizes the need for tailored strategies to enhance resource efficiency and renewable energy adoption. A global assessment using datasets from the World Bank and Our World in Data highlights disparities across regions, providing insights into region-specific opportunities and challenges….Read more