Homeless persons tend to die younger than the housed population and have complex, often unmet, end-of-life care needs. High levels of illicit drug use among this population are a particular challenge for health and social services professionals involved in end-of-life care services delivery. This article explores the challenges of end-of-life care services to homeless illicit drug users based on data collected during a national study on end-of-life care services delivery to homeless persons in Canada. The authors conducted qualitative interviews with 50 health and social services professionals involved in health services delivery to homeless persons in five cities. Interviews were transcribed verbatim and analysed thematically. Themes were organised into two domains. First, barriers preventing homeless illicit drug users from accessing end-of-life care services, such as competing priorities (e.g. withdrawal management), lack of trust in healthcare providers and discrimination. Second, challenges to end-of-life care services delivery to this population in health and social care settings, including non-disclosure of illicit drug use, pain and symptom management, interruptions in care, and lack of experience with addictions. The authors identify a need for increased research on the role of harm reduction in end-of-life care settings to address these challenges.