Balancing ecological priorities with economic outcomes in regulated river systems is a challenge in freshwater management. Designer flows—ecologically motivated water releases into highly regulated river segments—offer a promising yet costly approach to conserving threatened species and restoring ecosystems. In this study, we perform an integrated assessment of designer flow implementation at the Glen Canyon Dam on the Colorado River. This prominent example demonstrates how designer flows can control nonnative species that disadvantage endemic threatened species. However, our analysis suggests that the costs, driven by the high value of foregone hydropower, delays in ecological benefits, and uncertainties in effectiveness, currently outweigh the benefits. Our findings provide a framework for evaluating designer flow implementation in other regulated river systems, linking economic valuation to ecological outcomes. This study highlights the importance of interdisciplinary collaboration in natural resource management, informing freshwater valuation by connecting policy-relevant indicators to management practices.