A simulation-based fuzzy optimization method (SFOM) was proposed for regional groundwater pumping management in considering uncertainties. SFOM enhanced the traditional groundwater management models by incorporating a response matrix model (RMM) into a fuzzy chance-constrained programming (FCCP) framework. RMM was used to approximate the input–output relationship between pumping actions and subsurface hydrologic responses. Due to its explicit expression, RMM could be easily embedded into an optimization model to help seek cost-effective pumping solutions. A groundwater management case in Pinggu District of Beijing, China, was used to demonstrate the method's applicability. The study results showed that the obtained system cost and pumping rates would vary significantly under different confidence levels of constraints satisfaction. The decision-makers could identify the best groundwater pumping strategy through analyzing the tradeoff between the risk of violating the related water resources conservation target and the economic benefit. Compared with traditional approaches, SFOM was particularly advantageous in linking simulation and optimization models together, and tackling uncertainties using fuzzy chance constraints.