Abstract: With the gradual decrease in freshwater resources, the gradual increase in energy demand and the continuous change of food supply structure, coupled with the characteristics of both interdependence and competition among the three, the interaction of water-energyfood becomes more complex. In order to ensure water security, energy security and food security and achieve synergistic and optimal management of the three, the efficient use of resources and sustainable development, Ningdong Base, a drought-sensitive area combining resourcebased water shortage and seasonal water shortage, is taken as an example. This paper proposes a simulation model of water-energy-food system in Ningdong Base based on the Multi-Agent model, which constructs a simulation framework of water-energy-food in Ningdong Base by considering the water-energy-food system in Ningdong Base as a cooperative and symbiotic network system constituted by a number of relatively independent and autonomous Agents. The attributes of each Agent are defined, the interaction rules between Agents and between Agents and environmental elements were designed, and the water-energy-food simulation model of Ningdong Base is developed based on the MESA library, a multi-agent modeling tool in Python language, to simulate the system evolution process of Ningdong Energy and Chemical Base. The results show that with the growth of population, the water allocation, energy consumption and food consumption in the living department show a rising trend. The water allocation in the food department shows a changing trend corresponding to the change of crop yield.The water allocation in the energy department of the Ningdong Base shows a rising trend, and the annual growth of the water allocation in the prediction year is about 0.08 billion m~3. With the yearly growth of the area covered by ecological greening, the water allocation in the ecological department also shows an increasing trend year by year. The annual energy that can be delivered out of the base has a measured annual growth rate of about 19.85% and a predicted annual growth rate of about 3.53%, and is expected to increase to 4.96×10~7 tons of standard coal by 2025.