Abstract Background Cross-sectoral collaboration between healthcare and the social domain is necessary to address the complexity of health inequity. However, this collaboration is often unsustainable in the long-term, for example due to temporary budgets and professionals changing jobs. We explored the factors that facilitate or restrain sustainable cross-sectoral collaboration by applying an interdisciplinary theoretical lens combining insights from relevant frameworks from governance, interprofessional learning and health policy. Following, we applied the framework in an ‘Integrated Community Approach’ in two Dutch cities (Utrecht and Amersfoort). Methods A qualitative research was conducted, involving 32 semi-structured interviews with professionals involved in an ‘Integrated Community Approach’ in the two Dutch cities in 2022 and 2023. Participants worked at various levels of the municipality, or as a local professional in the medical or social domain in the community. Thematic analysis and a deductive approach were employed- based on the theoretical framework. Results We identified nine components as important for sustainable cross-sectoral collaboration. Whether these components acted as facilitator or barrier varied between participants, depending on their position and organizational context. The nine components could be summarized into three main mechanisms: 1) the foundation for collaboration, which is dependent on having a shared vision and the competencies to engage residents; 2) a pre-condition, which is having support at management level and having the right resources; 3) support, which is provided by data and flexibility. Conclusions Long-term cross-sectoral collaboration is important, complex and depends on various interconnected factors. To improve cross-sectoral collaboration in the long term, it is necessary to disentangle each theme and conduct in-depth analysis of each one individually to facilitate deeper understanding of the context and problem. Key messages • Collaboration between medical and social sectors is challenging, yet significance is clear. While the start is evident, sustaining the ‘how’ is unclear. • The opportunities and obstacles of cross-domain collaboration vary among stakeholders, influenced by both their organization and position within it.