This study explored how professionals in the field of social work recognize and respond to different forms of isolation in socio-economically marginalized neighborhoods in Sweden. Drawing on qualitative data from semi-structured interviews with six professionals, this study examined how spatial, social, cultural, and economic isolation manifest and interconnect within these neighborhoods. The data were analyzed using reflexive thematic analysis (RTA) method, applying empowerment theory and ecological systems theory. The authors’ findings indicated that isolation in marginalized areas is deeply rooted in structural inequalities, manifesting in factors such as segregation, stigmatization, and institutional incoherence. However, professionals combat these challenges through relationship-based approaches, empowerment, and local initiatives promoting community engagement and participation. Furthermore, this study emphasized the importance of context-specific, systemic, and collaborative response to isolation in the social work profession.