OBJECTIVE: To identify promising interventions targeting young people in East and Southern Africa through self-care practices, with a focus on prevention of unintended pregnancies and HIV and develop four evidence-based self-care models. METHODS: A structured literature review was conducted followed by a consultation with key stakeholders and youth networks from Malawi, South Africa, Zambia and Zimbabwe. Of the 2,890 published articles identified, 464 were fully reviewed and 59 were included in the final analysis along with 48 pieces of grey literature. A total of 31 youths participated in the consultation sessions. RESULTS: Self-care interventions with high levels of feasibility, acceptability, and scalability included HIV self-testing, self-management of contraceptives, and self-awareness for improved and safer sex behaviours and sexual health. Key features of these interventions included the use of non-clinical environments, regular follow ups to reinforce practice, use of digital solutions, linkage to in person care, and participatory approaches involving young people from ideation to implementation. CONCLUSION: Self-care models that promote distribution, access, support through multiple mechanisms in non-clinical environments are more acceptable and more effective in reaching young people.