Parental substance use is highly prevalent worldwide, presenting major child safeguarding and public health concerns. Qualitative research enables in-depth understanding of how young people experience parental substance use and helps inform practice and policy through illustrative cases of experiences. This review aimed to synthesize published qualitative evidence exploring the lived experiences, perceived impact, and coping strategies of children and young people whose parents use substances. International literature databases including Medline, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, International Bibliography of the Social Sciences, Social Science Database, Sociology Collection, and Scopus were searched from inception to 2022, alongside grey literature searching and relevant websites. Qualitative accounts were included, provided by participants aged below 25 years. No language, date, or geographical limits were applied. A thematic synthesis of 35 studies, across 49 papers, covering over 700 children and young people’s voices, identified five overarching themes. These themes included, (a) living with the unpredictable: insecurity within the family; (b) social and emotional impact of parental substance use; (c) controlling the uncontrollable: creating safety within the family; (d) coping with and resisting the emotional and social impacts; and (e) formal and informal support. The findings emphasize that children and young people who experience parental substance use are trying to manage and mitigate vulnerabilities and be resilient to unpredictable, adverse, and often stigmatizing experiences, usually without formal support in place. Further research is needed to coproduce child-centered interventions that promote children and young people’s social and emotional resilience.