Transitioning students with disabilities are at a disadvantage for post-school employment. This article explores ASPIRE case managers' roles in promoting employment among transition-age youth with disabilities receiving SSI. Qualitative and quantitative studies examined programmatic factors related to employment. Results showed that higher rates of face-to-face case management meetings and early employment experiences were associated with improved employment outcomes. Effective case managers' interactions with families were characterized by persistence, flexibility, and a holistic focus. Case management during the transition to adulthood, which crosses independent living, education, and employment domains, is important. A cross-domain case management model can be effective in mitigating multiple barriers to self-sufficiency experienced by families living with disability and poverty. Limitations and implications for research and practice are included.