The management of transboundary river basins across developing countries, such as the Lower Mekong River Basin (LMB), is frequently challenging given the development and conservation divergences of the basin countries. Driven by needs to sustain economic performance and reduce poverty, the LMB countries are embarking on significant land use changes in the form hydropower dams, to fulfill their energy requirements. This pathway could lead to irreversible changes to the ecosystem of the Mekong River, if not properly managed. This thesis aims to explore the potential effects of changes in land use —with a focus on current and projected hydropower operations— on the Lower Mekong River network streamflow and instream water quality. To achieve this aim, this thesis first examined the relationships between the basin land use/land cover attributes, and streamflow and instream water quality dynamics of the Mekong River, using total suspended solids and nitrate as proxies for water quality. Findings from this allowed framing challenges of integrated water management of transboundary river basins. These were used as criteria for selecting eWater’s Source modelling framework as a management tool that can support decision-making in the socio-ecological context of the LMB. Against a combination of predictive performance metrics and hydrologic signatures, the model’s application in the LMB was found to robustly simulate streamflow, TSS and nitrate time series. The model was then used for analysing four plausible future hydropower development scenarios, under extreme climate conditions and operational alternatives. This revealed that hydropower operations on either tributary or mainstream could result in annual and wet season flow reduction while increasing dry season flows compared to a baseline scenario. Conversely, hydropower operation on both tributary and mainstream could result in dry season flow reduction. Both instream TSS and nitrate loads were predicted to reduce under all three scenarios compared to the baseline. These effects were found to magnify under extreme climate conditions, but were less severe under improved operational alternatives. In the LMB where hydropower development is inevitable, findings from this thesis provide an enhanced understanding on the importance of operational alternatives as an effective transboundary cooperation and management pathway for balancing electricity generation and protection of riverine ecology, water and food security, and people livelihoods.