Background: Tenancy sustainment—the maintenance of a tenancy to avoid a premature end of tenure—is fundamental to homelessness prevention. Understanding what enables a successful tenancy is essential to inform interventions to support people leave homelessness. Objective: To conduct a systematic review to identify determinants associated with tenancy sustainment following homelessness. Search methods: A detailed search of 12 electronic databases, as well as grey literature sources, was conducted in 2015 and updated in 2016. The study protocol is registered with PROSPERO (CRD42015019361). Selection criteria: All study designs with a population of homeless or formerly homeless individuals, in which tenancy sustainment was the primary outcome were included. Abstract and full text review was carried out independently by two reviewers. The methodological quality of articles was assessed using QualSyst, a validated quality appraisal tool. Data collection and analysis: A data extraction form was developed for the review and was completed by two reviewers to ensure accuracy. The heterogeneity of included studies indicated that a narrative overview of the results was most appropriate. Main results: Forty three articles reporting 38 studies were included. The determinants were categorized at four levels: individual, interpersonal, community and structural. Participation in specific programs, for example Housing First, receiving social support and being older were identified as the possible determinants of tenancy sustainment. Author’s conclusions: This systematic review is the first, to our knowledge, to focus solely on tenancy sustainment as a primary outcome. A range of determinants associated with tenancy sustainment was identified but it was difficult to draw strong conclusions due to the heterogeneity of the studies. Despite being a fundamental concept in homelessness research, tenancy sustainment is poorly defined and conceptualised. A deeper understanding of tenancy sustainment will inform the development and evaluation of interventions that support people to leave homelessness and maintain tenancies. Public health implications: Housing stability is central to preventing homelessness and addressing the numerous public health concerns that can co-occur with homelessness. Our review highlights that a standardized approach to measuring housing stability and more high quality intervention studies are essential in future research.