The Mekong Delta region has been seriously affected by climate change, with increasing temperatures, sea-level rise, and salinization strongly impacting agricultural activities of the region. Recent studies have shown that groundwater exploitation also contributes significantly to land subsidence throughout the delta. Thus, combating climate change now makes it necessary to design strategies and policies for adapting to and mitigating climate change and subsidence, not only at the individual level (mainly farmers), but also at the institutional level (province and region). This study aims to build an integrated model for the purpose of exploring the socio-economic impact of adaptation strategies provinces choose under various climate and economic scenarios. The LUCAS–GEMMES model (an agent-based model for strategies for adapting to land-use change in the context of climate change) was developed in order to evaluate socio-economic factors, climate, and water use by farmers, as well as the subsidence dynamics and macroeconomic trends in land-use selection strategies. The simulations are carried out according to four main scenarios: (i) lack of provincial adaptation strategies and absence of subsidence dynamics, (ii) lack of adaptation strategies though subsidence and the impact of land-use production benefits, (iii) purely individual adaptation strategies combined with the impact of subsidence, and (iv) provincial and individual-scale adaptation combined with the impact of subsidence. In all the scenarios that consider subsidence, our results show that early response decisions to even low-level subsidence lead to many positive outcomes in water resource management, such as a significant reduction in water-use in the dry season and a reduction in the area vulnerable to subsidence and climate change. However, the same results also indicate a possible decrease in farmers’ income due to reduced agricultural seasons and restricted land-use transformation, which demonstrates the importance of modeling the multi-sectoral aspects of adaptation. Finally, at a more general level, in the fourth scenario, the model clearly shows the benefits when provinces located in the same agro-ecological zone harmonize strategies, thus paving the way for defining integrated land-use policies at the regional level.