Co-occurring mental health and substance use disorders are highly prevalent among individuals experiencing long-term homelessness. This paper describes strategies used by 11 projects funded by the Federal Collaborative Initiative to Help End Chronic Homelessness (CICH) to serve individuals with co-occurring disorders (COD) as they transition from homelessness to permanent-supported housing. Findings are based on the observations of clients, program team members, and administrators. This paper presents findings organized around three themes: characteristics and needs of CICH clients with COD, strategies employed to respond to those needs, and challenges associated with implementing an integrated approach to COD. Client characteristics include histories of untreated or intermittently treated mental health and substance use disorders, often further complicated by trauma and chronic illness. Project teams endorsed a variety of services and supports such as engagement, stabilization, motivational techniques, groups, and trauma-informed interventions as useful for their clients with COD. Challenges identified include difficult client behavior, the extended time required for change to occur within this population, inadequate staffing and community resources, and system barriers. The paper concludes with recommendations for further research into the effectiveness of various combinations of service strategies for this population in non-traditional settings during the earliest stage of recovery, along with a call for overcoming workforce and system-level barriers to providing integrated care.