In rivers around the world, hydropower development has altered the seasonal hydrological regime, which drives key ecosystem services. Dam re-operation efforts that minimize hydrological alterations are, therefore, critical to biological conservation, particularly in the tropics, where dam development is still booming. Here, we identify the limits and opportunities of alternative dam management strategies in the Mekong, a biodiverse but rapidly developing river. We show that basin-wide efforts are needed to completely restore seasonal hydrological variability, probably an unfeasible solution in the Mekong's institutional landscape. Instead, re-operation efforts focused on the Lower Mekong could yield tangible opportunities for partially restoring key elements of hydrological variability while preserving hydropower production. In fact, changing production plans across a few critical dams could raise hydropower revenues by almost $150 million per year. Nexus solutions like this one are a concrete basis for safeguarding crucial economic interests and catalyzing sustainable river management in international rivers.