Two established models for delivering services to people who are homeless and have complex health needs (including co-occurring disorders) are Assertive Community Treatment (ACT) and the Comprehensive, Continuous, Integrated System of Care (CCISC). This quasi-experimental study presents preliminary data comparing these ACT and CCISC. The first program was based out of a community mental health center and used the ACT model of care with supported housing (ACT-SH). The second program was based out of a substance abuse treatment agency and used the CCISC model of care in a residential treatment facility (CCISC-RT). Participants completed clinical assessment interviews at baseline before being admitted to the programs and then 6 months later. Measures included the Brief Symptom Inventory (BSI) to measure mental health symptoms; the Treatment Services Needed and Received (TSNR) to assess service needs, usage, and levels of unmet needs; and a tool assessing employment, housing, and past-month substance use. Participants in both interventions reported significant reductions in substance use and mental health symptoms, although a slightly greater reduction in mental health symptoms was associated with the CCISC-RT program. Six months following enrollment, participants in the ACT-SH program were more likely to own or rent their own residence, but both programs were associated with major improvements in housing stability. This study indicates that both the ACT and CCISC models of care can be successfully implemented to serve homeless individuals with behavioral health needs. The CCISC-RT program was based in a residential treatment facility and delivered a greater intensity of behavioral health services than the ACT-SH program, but results indicate that either approach can successfully be used to assist homeless individuals in obtaining a variety of needed services, reducing their substance use and mental health symptoms, and attaining a stable residence.