Cambodia’s Tonle Sap Lake will see major environmental changes due to the Mekong hydropower development. These changes have remarkable societal impacts, as the society is tightly connected with the physical geography through the lake’s unique flood pulse. Understanding the connections between water and livelihoods is, however, challenging due to the exceptional nature of the area and the gap between demographic and environmental information. As a result, the socio-economic drivers have been less analysed than the environmental changes. We addressed this research gap by assessing the status quo and recent trends in the area’s socio-economic setting with a spatial approach. The approach enabled presenting these trends and their linkages to the physical environment in a way that conventional, administrative boundaries-bound assessments are not able to do. We found that the economic activity structure changed relatively modestly between 1998 and 2008, with the proportions of the workforce within fishing and agriculture slowly decreasing. Yet, due to population growth, there was a significant increase of 140,000 people in these sectors. Our approach illustrated the spatial heterogeneity of the key socio-economic trends, underlining the significant changes occurred particularly in Siem Reap. The results also revealed an on-going ‘youth wave’ that brings a major demographic challenge – but also an opportunity – for both urban and rural areas and also puts additional pressure on natural resources. When planning the future development in the area, the demographic transition and key socio-economic trends must be considered hand in hand with the expected environmental impacts of hydropower development and climate change.