People experiencing homelessness often use substances. They may face barriers to reducing substance use while living in hostels. The review aimed to synthesise and assess the quality of existing qualitative research to address: How do people who use substances experience accessing and living in homeless hostels? Do hostels support or hinder behavioural change? Eligibility criteria were peer-reviewed, qualitative evidence from adults experiencing homelessness and substance use in the United Kingdom. Seven electronic databases were systematically searched. The Critical Appraisal Skills Programme qualitative checklist was used to assess the risk of bias. Interpretative meta-ethnography was used to synthesise reported findings. Eight reports were identified with 143 participants in total. Data collection was via semi-structured interviews and either thematic or framework analysis was used. Four third-order themes were developed: 1). Living in fear; 2). The power of human connection; 3). The need for emotional safety; and 4). The use of restrictive practices (subthemes: Rules take away choices; Infantilisation). The findings highlight people’s need for physical and emotional safety to seek support that can lead to exiting homelessness and recovering from substance use. A lack of safety can perpetuate substance use and, in turn, homelessness. Thus, a core response to alleviate homelessness paradoxically perpetuates the issue for some individuals.