This paper presents a multi-objective optimization model for the optimal design of a resilient macroscopic system that incorporates the water-energy-food nexus targeting economic and environmental objectives. The model aims to properly satisfy and distribute water and energy for agricultural, domestic, industrial, and livestock sectors, also it takes into account the treatment of wastewater from agriculture, domestic and industrial sectors, as well as the use of agricultural wastes to be used as fuel in power and desalinization plants. The model was coded and solved in the software GAMS. A case study from the northwest part of Mexico was considered to show the applicability of the proposed approach. Results show that it is possible to obtain resilient solutions in satisfying water, energy and food needs with an appropriated distribution of resources, even when the climatic conditions are extreme. (C) 2020 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.