A holistic approach to the management of water, energy, food, and the environment is required to both meet the socioeconomic demands of the future as well as sustainable development of these limited resources. The Urmia Lake Basin has faced environmental, social, and economic challenges in recent years, and this situation is likely to worsen under the impacts of climate change. For this study, an adaptability analysis of this region is proposed for the 2040 horizon year. Two models, the water evaluation and planning (WEAP (Stockholm Environmental Institute, Stockholm, Sweden)) and the low emissions analysis platform (LEAP (Stockholm Environmental Institute, Boston, MA, USA)), are integrated to simulate changes in water, energy, food, and the environment over these 20 years. Two climate scenarios and nine policy scenarios are combined to assess sustainable development using a multi-criteria decision analysis (MCDA) approach. Results show that, through pursuing challenging goals in agricultural, potable water, energy, and industrial sectors, sustainable development will be achieved. In this scenario, the Lake Urmia water level will reach its ecological water level in 2040. However, social, technical, and political challenges are considered obstacles to implementing the goals of this scenario. In addition, industry growth and industry structure adjustment have the most impact on sustainable development achievement.