Groundwater is a critical source of water supply for a variety of sectors, but is notoriously difficult to represent in large-scale, multisectoral models owing to the myriad of complex dynamics that dictate its economic and physical viability as a resource. A better understanding of the feasibility of groundwater in fulfilling that role requires an integrated hydro-economic evaluation of its cost and availability. To address this, we have developed a physics-based hydro-economic model, called Superwell, which generates grid cell-level estimates of extractable groundwater volumes and cost of production (including capital, maintenance, and energy costs). The fast, flexible, and robust modeling routine produces groundwater resource cost-supply curves that can be used within a range of integrated analyses. We demonstrate broad application of groundwater supply-cost curves using three exhibit studies, i.e., a global groundwater withdrawals study, a farm agent-based study, and a multisector dynamics study. In the first study, informed by the excessive extraction costs and reaching environmental limits from Superwell, projections of groundwater withdrawals into the future reveal a peak-and-decline signature, not observed previously in projections by studies without a cost-supply relationship and human-earth system integration. In another application of Superwell within a large-scale coupled farm-groundwater modeling framework, integration of cost curves into an agent-based modeling approach helped evaluate irrigation and farmer cropping dynamics given farm response to evolving groundwater conditions under future economic and water availability scenarios. Finally, in another study using scenarios of groundwater depletion from Superwell, the depletion limits and associated increases in water prices have shown groundwater-induced agriculture feedback to expand rainfed agriculture globally and shift irrigation crop production toward regions with relatively inexpensive water resources. Taken together, and as demonstrated, this capability unlocks the possibility of evaluating cost and extraction-dependent interactions of groundwater within energy-water-land systems, enabling the exploration of multisector dynamics within integrated human-Earth systems.