Climate change is projected to exacerbate extreme weather events in the South Asia, particularly Bangladesh’s Teesta River Basin (TRB), disrupting agriculture, food security, and livelihoods for millions of people. While local adaptation strategies can mitigate climate risks and reduce crop loss, the upfront costs can be a major concern for resource poor farmers. This study evaluated various adaptation measures using cost–benefit analysis and sustainability indicators. Results show that strip tillage wheat cultivation, short-duration rice varieties, and deep tube well-based irrigation systems offer higher net farm revenues, with all options presenting benefit–cost ratios greater than one—signaling profitable investment. In addition, practices such as alternate wetting and drying (AWD), zero tillage for mustard, and strip tillage wheat have the potential to reduce greenhouse gas (GHG) emissions moderately to significantly. Despite these promising results, several challenges remain that limit the potential, including limited farmer awareness, dependence on traditional irrigation, lack of machinery, limited access to credit, and high installation costs for deep tube wells. The study highlights low adaptive capacity in the TRB due to poor performance on economic, social, and environmental indicators. It emphasizes the need for strategic planning, financial support, subsidies, improved market access, and mechanization to scale up adaptation, reduce loss and damage, and boost resilience in South Asia.