Out-migration is of high concern for rural communities in many deltas around the world, that are under the pressure of drought and saltwater intrusion (DSI). In the coastal provinces in the Vietnamese Mekong Delta (VMD), DSI driven by climate change has forced farmers to migrate to large cities for new livelihoods. This paper assesses the migration mechanism in Soc Trang province in the VMD, evaluating the perspectives of 120 farmers and 10 local officials interviewed in four communities. A framework of livelihood vulnerability index (LVI) was used to evaluate the vulnerability of farmers related to the intensifying DSI. A Strengths−Weaknesses−Opportunities−Threats (SWOT) analysis has been followed to assess the rural labor out-migration linked to livelihood sustainability perspectives of farmers before a Threats−Opportunities−Weaknesses−Strengths (TOWS) matrix was used to explore labor management strategies. Our results indicate that farmers’ livelihoods are not sustainable due to the high negative impacts of DSI, resulting in low marginal profits from rice production, but low remittances by the migrants. The SWOT and TOWS analysis reveals that Weaknesses−Strengths is the most promising strategy for providing jobs and loan development programs for the out-migration issue. These imply concreted policies for sustainable agricultural management and adaptation strategies to address the rural out-migration under the impact of the DSI. Our findings not only assess the mechanism of rural out-migration in coastal areas of the most vulnerable delta, but also offer an empirical evidence-based strategy for the labor out-migration issue due to DSI driven by climate change.