Trauma can be both a cause and a consequence of homelessness and has lasting impacts on mental health and wellbeing. Often research focusses on trauma and adversity in childhood leading to homelessness, but understanding traumatic experiences during adulthood homelessness can be just as important for informing intervention development and policies to mitigate and eradicate homelessness. Working with people with lived experience of homelessness, this review aimed to synthesis the qualitative evidence exploring the impact of trauma during homelessness on mental health (including substance use) from the perspective of adults (18 years of age and older) experiencing homelessness. Alongside gray literature, ASSIA, CINAHL, Cochrane, EMBASE, MEDLINE, Proquest theses and dissertations, PsychInfo, Scopus and Web of Science were searched from inception until February 2024. No language, date, or geographical limits were applied. A ‘best-fit’ framework synthesis of 26 papers, covering the experience of over 900 people, identified three overarching themes linked with the SAMHSA three E’s of trauma: 1) making sense of homelessness as a trauma, 2) dealing with the impacts of trauma and 3) responses to repeated exposure to trauma. Trauma rarely takes place in isolation and often prior experiences shape how people experiencing homelessness make sense and cope with trauma. Policy and prevention should prioritise early intervention to reduce the mental health burden of trauma and homelessness. Additionally, creating support that empowers and builds resilience will encourage more positive management strategies.