The coastal area of Bangladesh has been a focus of climate change and hazard research due to its extreme vulnerability to tropical cyclones, often leading to disaster. Little is known about how other key stressors, interacting with these extreme weather events, impact on natural resource base and flow of ecosystem services that sustain local livelihoods. In this paper, we explore the process by which major stresses and hazards shape the vulnerability of people’s livelihoods in dynamic social-ecological environments in the southwest coastal region in Bangladesh. Drawing on qualitative and quantitative data from a case study, we identify the key drivers of change in social-ecological systems and evaluate whether these drivers have affected livelihood outcomes and various components of human wellbeing. This analysis suggests that together, increasing salinity intrusion, tropical cyclone and land-use change (directly and through changes in ecosystem services) affect the access to livelihood assets at household scale and undermine social wellbeing by seriously impacting food and water security. Through identification of key stresses, interactions, and process of altering ecosystems and various forms of household capitals, the current study proposes a conceptual framework to understand the present day vulnerability to multiple stressors in the context of the coastal region in Bangladesh.