As the backbone of Vietnam’s economy, the country has recently established a number of policies for promoting and investing in smart agriculture in the Mekong Delta, the country’s largest agricultural hub, to foster overall socio-economic development. However, water remains a critical constraint for crop production, with progress being hindered by water scarcity and quality issues, and compounded by socio-economic transformation and climate change. Considering these challenges, this study used the CROPWAT model and a wide spectrum of climate change scenarios to investigate future total water demands in the 2030s and 2050s as well as drought levels in two underdeveloped semimountainous reservoir catchments, i.e., O Ta Soc and O Tuk Sa in An Giang province. The results suggest that the usable storage capacity of the O Ta Soc reservoir will increase to 650,000 m3 to meet water supply demands under all climate change scenarios and the medium-term, moderate drought conditions. The useable storage capacity of the O Tuk Sa reservoir will also be increased to 880,000 m3 and the irrigation area would see a marked 70% reduction compared to its design irrigation. Under these circumstances, the O Tuk Sa reservoir will continue to supply water under all climate change scenarios and medium-term droughts. As a core element for strategic planning and to ensure efficient management of water resources, the results highlight the importance of estimating potential runoff and rainfall in semi-mountainous reservoir catchments under various drought conditions in order to propose the suitable expansion of the useable water storage capacities