North-to-south migration has been a persistent trend in Ghana. Yet the migrating population has recently shifted to become predominantly female and younger, with a significant increase in rural adolescent girls seeking employment in urban and peri-urban areas. For adolescents without strong networks of social and financial support, this practice can jeopardize their physical and mental health, putting them at risk of sexual victimization and economic exploitation. Building upon the work of cumulative risk and ecological systems theorists, this article examines the case of female adolescent load bearers (Kayayei) in Ghana, highlighting the need to develop and evaluate multi-component prevention efforts.