 The Mekong River Basin is a vital resource for millions of people and ecosystems, but it is undergoing rapid environmental degradation due to climate change and human activity. To address these challenges, we have compiled a comprehensive dataset of climate, hydrology, ecology, and socio-economic data from multiple sources. This data provides valuable insight into surface water systems, groundwater dynamics, land use patterns, and socio-economic changes. It can be used to inform science-based decision-making and policy development for sustainable food energy water, livelihood, and ecological systems in the Mekong River Basin. This article was authored by M. R. Deepthiwari, Yadu Pokral, Daniel Kramer, and others.