Intersections of food, energy, and water systems (also termed as the FEW nexus) pose many sustainability and governance challenges for urban areas, including risks to ecosystems, inequitable distribution of benefits and harms across populations, and reliance on distant sources for food, energy, and water. This case study provides an integrated assessment of the FEW nexus at the city and regional scale in ten contiguous counties encompassing the rapidly growing Denver region in the United States. Spatial patterns in FEW consumption, production, trans-boundary flows, embodied FEW inputs, and impacts on FEW systems were assessed using an urban systems framework for the trans-boundary food-energy-water nexus. The Denver region is an instructive case study of the FEW nexus for multiple reasons: it is rapidly growing, is semi-arid, faces a large projected water shortfall, and is a major fossil fuel and agricultural producer. The rapid uptake of high-volume hydraulic fracturing (HVHF) combined with horizontal drilling in populated areas poses ongoing risks to regional water quality. Through this case study, fracking is identified as a major topic for FEW nexus inquiry, with intensifying impacts on water quantity and quality that reflect nationwide trends. Key data gaps are also identified, including energy for water use and food preparation. This case study is relevant to water and sustainability planners, energy regulators, communities impacted by hydraulic fracturing, and consumers of energy and food produced in the Denver region. It is applicable beyond Denver to dry areas with growing populations, agricultural activity, and the potential for shale development.