Young people in residential out-of-home care often exhibit health and psychosocial challenges, which can emerge from childhood trauma. A body of research has examined the wellbeing of these young people; however, the ways in which interventions and practice models can improve the health and psychosocial wellbeing of young people in out-of-home care remains unclear. A systematic review was conducted to examine the effectiveness of interventions and practice models for improving health and psychosocial outcomes of young people in residential care and to identify relevant knowledge gaps. After a worldwide search, only four studies, from Australia (n = 2), USA (n = 1), and Canada (n = 1) were found. These studies evaluated Cognitive Behaviour Treatment, Healthy Eating Active Living, Power Through Choices and the Alternate Care Clinic. These studies aimed to improve numerous health and psychosocial outcomes including mental health, behaviour, obesity, pregnancy and sex. Despite limited evidence, the review suggests that contemporary interventions and practice models do have the potential to have positive impacts on the health and psychosocial outcomes of young people in residential care. Rigorous assessment of promising evidence-based interventions is urgently needed to advance best practice and improve outcomes.