Abstract: Under changing environmental conditions, water-scarce basins are facing increasingly severe conflicts between water supply and demand. Therefore, there is an urgent need to innovate and develop methods and technologies to regulate water resource resilience during extreme drought years. This study focuses on enhancing the resilience of water resource systems. An evaluation method for the resilience of basin water resource systems has been established by considering their robustness, resistance, and recovery capacities. Multi-source water potential tapping measures and thresholds have been proposed for the Yellow River basin during extreme drought years, including reservoir group interannual water replenishment, flexible groundwater extraction, and water diversion along the Eastern and Middle Routes of the South-to-North Water Diversion Project for enhanced supply. With the objective of maximizing basin water resource system resilience and the constraints of basin production-living-ecological baseline water demand, river discharge requirements, and multi-source water potential tapping limitations, a resilience regulation model for water resource systems in the Yellow River basin have been developed. The effects of different combinations of measures on system resilience have been analyzed to propose investment strategies for enhancement measures, and optimize the allocation relationship between ecological and socioeconomic water uses. Therefore, water security is guaranteed during extreme droughts. These findings indicate that, under the 2002 extreme drought scenario with current water use practices in 2022, the functions of water resource systems would be severely damaged without interventions. The baseline water demands are determined using the basin water demand hierarchy. The critical threshold for resilience regulation has been identified as 0.46, with the optimal proportion of instream ecological water use ranging between 21%—26%. Resilience regulation strategies during extreme drought years involve the water diversion of the Eastern and Middle Routes of the South-to-North Water Diversion Project, flexible groundwater extraction, and reservoir group interannual water replenishment to enhance supply.