<p>In the context of globalization and regional development, water, energy, and food (WEF) are the cornerstone of social development. However, major grain-producing regions face imbalances between the supply and demand of WEF resources while ensuring national food security. Addressing these imbalances is crucial for achieving the United Nations Sustainable Development Goals (SDGs). In this study, a Water-Energy-Food-Society-Economy-Environment (WEF-SEE) system dynamics model (SDM) is constructed to explore the sustainable development of major grain- producing regions. Taking Henan Province in China as case study, the results show that: (1) Increasing the irrigation water effective use coefficient by 20% reduces agricultural water consumption by 16%, raising the Water Security Index (WSI) from 1.046 to 1.109 by 2030. (2) With constant total cultivated area, increasing the proportion of corn cultivation to 50% raises Henan’s contribution to national grain production from 10.38% to 10.45%. Henan’s contribution to national grain production remains above 10% by 2030. Expanding the total cultivated area increases grain output by 16%, boosting the Food Security Index (FSI) from 1.39 to 1.72, but also leads to a 16% increase in energy consumption. (3) While policies that promote renewable energy and reduce primary energy production improve energy security in the long term, CO₂ emissions would still increase in the short term. (4) Policies aimed at raising population growth can help mitigate rural labor aging, but the associated increases in domestic water and energy consumption negatively affect both the WSI and the Energy Security Index (ESI).</p> Graphical abstract <p></p>