The water–energy–food nexus (WEF nexus) concept is a novel approach to manage limited resources. Since 2011, a number of studies were conducted to develop computer simulation models quantifying the interlinkage among water, energy, and food sectors. Advancing a nationwide WEF nexus simulation model (WEFSiM) previously developed by the authors, this study proposes an optimization module (WEFSiM-opt) to assist stakeholders in making informed decisions concerning sustainable resource management. Both single- and multi-objective optimization modules were developed to maximize the user reliability index (URI) for water, energy, and food sectors by optimizing the priority index and water allocation decisions. In this study, the developed models were implemented in Korea to determine optimal resource allocation and management decisions under a plausible drought scenario. This study suggests that the optimization approach can advance WEF nexus simulation and provide better solutions for managing limited resources. It is anticipated that the proposed WEFSiM-opt can be utilized as a decision support tool for designing resource management plans.