<p>Vulnerability assessment is essential for creating strategies for risk reduction and mitigation. In Sundarban Biosphere Reserve, no one has studied the socio-economic vulnerability index using site-specific indicators for the Indigenous agrarian community. By evaluating relative regional socio-economic vulnerability at the village level, identifying priority regions for mitigating the effects of climate change-induced vulnerability, and developing appropriate policies using a mixed-method approach, the current study will be very helpful in filling this research gap. This study performed six focus group discussions and surveyed 300 randomly selected tribal households using a multi-stage stratified random sample procedure. This study utilized 64 indicators under 14 major components and used the IPCC framework to measure the socio-economic vulnerability to climate change in the ISBR. Results indicate that Sukdoani (0.917) has the highest socio-economic vulnerability score, followed by Gangasagar (0.797), Chanpali Abad (0.744), Kachurula (0.739), and Khasramkarer Chak (0.719). The lowest socio-economic vulnerability score has been found in Jay Khali (0.289), followed by Palpur (0.410) and Shyamnagar (0.491). A high level of vulnerability was found due to a higher rate of exposure and sensitivity and a lower rate of adaptive capacity. However, it is observed that village location plays a very important role in vulnerability as the highly vulnerable villages are located very close to the river bank. The village location and infrastructure facilities, institutional facilities, and health and sanitation conditions play crucial roles in vulnerability. Other parts of India and other developing nations can use this approach at various scales.</p> Graphical abstract <p></p>