As individuals with Down syndrome (DS) are living longer, there is a growing need to support this population across the lifespan. In particular, the transition out of high school marks a critical time point that sets the course for the rest of adulthood, especially for the outcomes of community-based living, post-secondary education, employment, and community engagement. Little is known about these outcomes in adults with DS, who may experience unique post-school challenges and opportunities relative to those with other intellectual and developmental disabilities. In this paper, we review the state of the literature on post-high school transition outcomes in DS and infuse a phenotypic approach to highlight individual and environmental characteristics associated with these outcomes. We also emphasize current service delivery needs and gaps in the evidence base that must be addressed in order to best support this population during the critical post-high school transition period.