This article reports social workers’ attitudes and approaches to working with people experiencing multiple exclusion homelessness (MEH) who self-neglect, and whether these people receive services, including safeguarding, differently from other populations. It draws on telephone interviews in 2020 with twenty-two social workers working with adults in a range of statutory local authority and National Health Service hospital roles in England. Interviews used two almost identical vignettes featuring self-neglect to prompt discussion and solicit experiences; one included homelessness and drug use to draw out any differences. Following transcription, interview data were analysed thematically. What emerged is a rich understanding of practice responses to self-neglect, but also uncertainties within contemporary social work: whether people who are homeless fall under the ‘umbrella’ of Adult Social Care and safeguarding; and whether self-neglect ‘fits’ under safeguarding. Additionally, participants described barriers to successful multi-agency support for people experiencing MEH, including stigma and exclusion from some statutory services. There was evidence that recent learning from Safeguarding Adults Reviews and local deaths has led to some examples of stronger multi-agency working in this context. The findings suggest more clarity is needed within the profession to ensure that people experiencing MEH benefit from strengthened social work input and safeguarding expertise.