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Sustainable provisioning of energy to society requires consideration of the nexus between food–energy–water (FEW) flows while meeting human needs and respecting nature's capacity to provide goods and services. In this work, we explore the FEW nexus of conventional and techno-ecologically synergistic (TES) systems by evaluating combinations of various technological, agricultural, and ecological strategies from the viewpoints of electricity generation, food production, life cycle water use, carbon footprint, nutrient runoff, corporate profitability, and societal well-being. We evaluate activities related to power generation (coal and gas extraction and use, transportation options, cooling technologies, solar panels, wind turbines), food production (farming with and without tillage), waste utilization (carbon dioxide capture and conversion to hydrocarbons, green hydrogen), and ecological restoration (forests and wetlands). Application of this framework to the Muskingum River watershed in Ohio, U.S.A. indicates that seeking synergies between human and natural systems can provide innovative solutions that improve the FEW nexus while making positive contributions to society with greater respect for nature's limits. We show that the conventional engineering approach of relying only on technological approaches for meeting sustainability objectives can have limited environmental and societal benefits while reducing profitability. In contrast, techno-ecologically synergistic design between agricultural systems and wetlands can reduce nutrient runoff with little compromise in other goals. Additional synergies between farming and photovoltaic systems along with the use of wetlands can further improve the FEW nexus while reducing CO 2 and nutrient emissions, with a relatively small compromise in corporate profitability. These results should motivate further work on innovative TES designs that can provide “win–win” solutions for meeting global energy needs in an environmentally and socially beneficial manner.