Siloed-approaches may fuel the misguided development of hydropower and subsequent target-setting under the sustainable development goals (SDGs). While hydropower development in the Indus basin is vital to ensure energy security (SDG7), it needs to be balanced with water use for fulfilling food (SDG2) and water (SDG6) security. Existing methods to estimate hydropower potential generally focus on: only one class of potential, a methodological advance for either of hydropower siting, sizing, or costing of one site, or the ranking of a portfolio of projects. A majority of them fall short in addressing sustainability. Hence, we develop a systematic framework for the basin-scale assessment of the sustainable hydropower potential by integrating considerations of the water-energy-food nexus, disaster risk, climate change, environmental protection, and socio-economic preferences. Considering the case of the upper Indus, the framework is developed by combining advances in literature, insights from local hydropower practitioners and over 30 datasets to represent real-life challenges to sustainable hydropower development, while distinguishing between small and large plants for two run-of-river plant configurations. The framework first addresses theoretical potential and successively constrains this further by stepwise inclusion of technical, economical, and sustainability criteria to obtain the sustainable exploitable hydropower potential. We conclude that sustainable hydropower potential in complex basins such as the Indus goes far beyond the hydrological boundary conditions. Our framework enables the careful inclusion of factors beyond the status-quo technological and economic criterions to guide policymakers in hydropower development decisions in the Indus and beyond. Future work will implement the framework to quantify the different hydropower potential classes and explore adaptation pathways to balance SDG7 with the other interlinked SDGs in the Indus.