Trade-offs between socio-economic growth and environmental protection have remained a critical issue of sustainable development, especially in the Global South. In the floodplains of the Vietnamese Mekong Delta (VMD), the development of high-dike polders for intensive rice production has degraded ecosystems and changed socio-economic patterns. Sustainable development pathways must be considered during policy formulations to keep pace with such transformations. In this study, the interwoven socio-economic development and rice-based agricultural production processes were assessed based on mixed data sources, including 550 interviews with farmers in two major delta floodplain provinces — An Giang and Dong Thap. It highlights the pros and cons of the triple-rice farming systems under high-dike protections compared to low-dike farming systems. Results showed that the environmental degradation due to the overuse of agrochemicals (e.g., fertilizer and pesticides) costs approximately US $565 per hectare per crop season, resulting in the lower marginal benefits for the triple-rice production compared to the double-rice production pattern. This includes higher costs borne by local farmers/communities, given the adverse effects of agrochemicals on their health. The study urgently calls for local governments to consider relevant drivers of environmental degradation in agricultural production, especially in rice cultivation. Future policy needs to consider whether the intensification in agriculture, such as triple-rice production, would be an appropriate development pathway for the rural economy. Our study conveys to central and local governments and associated stakeholders that the agriculture-driven development policies would not be a sustainable development pathway under new environmental complexities in the delta.