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Three-dimensional transient groundwater flow and saltwater transport models were constructed to assess the impacts of groundwater abstraction and climate change on the coastal aquifer of Tra Vinh province (Vietnam). The groundwater flow model was calibrated with groundwater levels (2007–2016) measured in 13 observation wells. The saltwater transport model was compared with the spatial distribution of total dissolved solids. Model performance was evaluated by comparing observed and simulated groundwater levels. The projected rainfalls from two climate models (MIROC5 and CRISO Mk3.6) were subsequently used to simulate possible effects of climate changes. The simulation revealed that groundwater is currently depleted due to overabstraction. Towards the future, groundwater storage will continue to be depleted with the current abstraction regime, further worsening in the north due to saltwater intrusion from inland trapped saltwater and on the coast due to seawater intrusion. Notwithstanding, the impact from climate change may be limited, with the computed groundwater recharge from the two climate models revealing no significant change from 2017 to 2066. Three feasible mitigation scenarios were analyzed: (1) reduced groundwater abstraction by 25, 35 and 50%, (2) increased groundwater recharge by 1.5 and 2 times in the sand dunes through managed aquifer recharge (reduced abstraction will stop groundwater-level decline, while increased recharge will restore depleted storage), and (3) combining 50% abstraction reduction and 1.5 times recharge increase in sand dune areas. The results show that combined interventions of reducing abstraction and increasing recharge are necessary for sustainable groundwater resources development in Tra Vinh province.