The karst area of Meixi River Basin in Chongqing is abundant in groundwater resources. Research on the genetic model of the water-bearing system and the water resource environment is crucial for the sustainable development of the karst water resources in the Yangtze River Economic Belt. The groundwater environment in the Meixi River Karst Basin exhibits good quality and holds significant potential for exploitation and utilization. Hydrogeological parameters were assigned based on the spatial distribution of stratum lithology, utilizing surface water systems as units. An evaluation of karst groundwater resources was conducted within the subsystem, providing a scientific basis for the assessment and management of karst water resources. Assessments of karst groundwater resources in the Meixi River Basin indicate that the average annual groundwater runoff in the Wenfeng River Basin is 4 562.07×10⁴ m³/a, with groundwater storage resources amounting to 22 540.10×10⁴ m³/a, and extracted resources totaling 2 027.42×10⁴ m³/a. In the main stream basin of the Meixi River, the average annual groundwater runoff is 6 769.66×10⁴ m³/a, groundwater storage resources are 32 062.08×10⁴ m³/a, and exploitable resources are 2 917.38×10⁴ m³/a. These research findings provide a scientific basis for the sustainable development of the karst water resources environment in the Yangtze River Economic Belt in Chongqing.