Objectives: We sought to understand the stressors, the parent-child relationship and family processes, and experiences with services among families experiencing parental substance use disorders (SUDs) and homelessness. Methods: We conducted a total of 41 in-depth semistructured interviews with parents with a history of SUDs and homelessness (n = 16) and housing support staff (n = 25) from May 2017 until January 2018. Participants were recruited from transitional housing facilities across the Los Angeles metropolitan area, which served families experiencing homelessness and parental SUDs. The interviews were audio-recorded, transcribed, and themes coded with Dedoose. Results: We found a high burden of trauma and guilt among parents, and a fear of SUD disclosure. We found challenges with family processes important for SUD prevention, including communication, discussion of substance use, and family and youth goal setting. We also discovered unique stressors related to navigating housing and services within the community. Conclusion: Our findings demonstrate the need for a family-based SUD-preventive intervention for youth growing up in families with parental SUDs and experiencing homelessness, to address the heightened SUD risk. In addition, findings from our study can inform clinical and housing services for this important population.