Children going missing from local authority care present significant safeguarding challenges, yet little is known about how care home staff perceive and respond to these incidents. This study explores perspectives and experiences of care home staff and managers (CHS/Ms) regarding factors facilitating or hindering the prevention of, and response to, children who go missing from care. Thematic analysis of fourteen interviews highlighted five key themes: (1) multi-agency communication and collaboration, (2) child-centred responses, (3) relationships with children, families, and communities, (4) professional skills and organizational support, and (5) timely and effective Return Home Interviews (RHIs). Findings emphasize the centrality of trauma-informed, relational, and child-centred approaches, alongside well-supported staff and coordinated multi-agency practice, in preventing missing episodes and ensuring safe returns. Barriers included inconsistent communication, resource constraints, procedural variation, and challenges in building trust with children and partner agencies. Findings provide actionable recommendations for practitioners and policymakers, highlighting the importance of consistent staffing, flexible frameworks, relational practice, structured training, and robust systems for information-sharing and RHIs. Insights contribute to the evidence base on safeguarding looked-after children and underscore the need for integrated, practice-informed strategies to reduce risk and improve outcomes for children who go missing from care.