Cross-sector collaborations (CSCs) are crucial for addressing complex environmental, social, and economic challenges. Sustainability issues are multifaceted and require holistic solutions that leverage multiple stakeholders’ expertise, perspectives, resources, and networks. This research explores the effectiveness of CSCs for strategic sustainable development (SSD). It identifies conditions for effective sustainability-oriented CSCs, assesses the applicability of these findings to various contexts, and provides key considerations for newly forming CSCs and SSD practitioners. The research study was undertaken in two phases. Phase 1 examined cross-sector initiatives within the sustainable development field in Sweden and other parts of Europe. It explored how these CSCs operate effectively by examining their formation conditions, processes and structures, endemic tensions and conflicts, and accountabilities and outcomes using a conceptual framework. Data collection involved nine semi-structured interviews, which were analysed deductively to identify patterns based on these conditions. In phase 2, the findings from phase 1 were summarised and presented to SSD practitioners working with CSCs. This phase refined the nuances CSCs need to effectively apply a strategic sustainable development approach. Data collection involved semi-structured interviews, and the findings were analysed inductively to pinpoint common themes. The research identified eight key considerations for SSD practitioners when working with CSCs toward sustainable development.