Global primary and secondary resources are important for economic growth. Resource management and environment conservation are currently frequently discussed topics worldwide. In this study, a discrete optimization model formulation is presented for an integrated energy, water, and food (EWF) supply chain problem. The optimization model examines the temporal and spatial integration of the EWF supply chain elements to provide optimal infrastructure capacity expansion of essential commodities within the EWF system, and their corresponding periodic optimal supply for a given region. Furthermore, the model considers endogenous demand between the EWF elements that reflect the interdependency of nexus elements. A mixed integer linear programming model is developed to assist in the process of optimal infrastructure capacity expansion and operation of the EWF system. A case study is given to show the application of the proposed mathematical programming model. Several scenarios are assumed for the case study under different commodity prices and climate change conditions. In addition, diversification in the energy and agriculture sectors is examined by shifting from international refined sugar trading to bioethanol production. The results show economic gains of similar to 10% under the emergence of bioethanol production compared with the business-as-usual scenario. Production dynamic exits for the production of refined sugar, bioethanol, and power from sugarcane and bagasse resources over time in the considered sale price range for the refined sugar and bioethanol products.