Self-neglect calls for collaborative inter-agency practice, but also presents distinctive challenges to collaboration, which are well-documented in practice reviews and research. Much existing research in this area has focused exclusively on social work perspectives on interprofessional collaboration. Work is needed that takes a more systemic approach, incorporating perspectives from other professions and services, to support more effective joint working. This article reports on a realist interview study that aimed to understand the mechanisms that underpin successful inter-agency collaboration in support of people experiencing self-neglect, and the barriers to achieving it. Based on semi-structured interviews with seventy-eight practitioners from Adult Social Care, Health, Housing, Fire & Rescue, and Environmental Health, sixteen people with experience of self-neglect, and two family carers, the study proposes nine principal programme theories of inter-agency dynamics under the headings of: policies and procedures; mutual inter-agency understandings of roles and task; keeping a collective shared focus on the person experiencing self-neglect; and support from management. It is argued that professional curiosity in safeguarding must be complemented by greater ‘inter-professional curiosity’ if inter-agency working is to fulfil its potential contribution to improving the lives of people experiencing self-neglect.