Climate change and growing demand pressures are motivating urban water utilities to explore cooperative water supply investment and management strategies. Recent work emphasizes the importance of dynamic and adaptive pathway policies when seeking to balance water supply reliability, financial stability, and equity objectives for cooperating regional utilities. Theoretically, regional cooperation agreements offer utilities better resource efficiency and supply reliability while limiting their individual and collective financial risks. However, cooperative implementation uncertainties may drive counterparty risks and exacerbate collaborating partners’ vulnerability to climate change and demand pressures. Cooperating utilities may also be exposed to performance and robustness degradations induced by partnering utilities’ actual implementation of complex cooperative infrastructure investment and water supply management actions. To address these concerns, this study formally characterizes the effects of implementation uncertainty within cooperative regional water supply investment and management pathway policies. We introduce the Safe Operating Spaces for Deeply Uncertain Pathway (DUSOS Pathways) framework, which is demonstrated on the Sedento Valley test case. We characterize the path-dependency of implementation uncertainties in short-term operational drought mitigation instruments and long-term infrastructure investment pathway policies. We delineate safe operating spaces to guide utilities’ actual portfolio implementation and facilitate cooperation between utilities to reduce the impacts of robustness degradation, increased vulnerability to demand-driven uncertainty in the face of challenging deeply uncertain futures, and altered investment pathways of new supply infrastructure. Overall, this methodology is broadly applicable to regional systems seeking to navigate complex cooperative regional water supply investment and management pathway policies.