Multisystemic Therapy® (MST®) is an intensive, home-based intervention for families of youth with social, emotional, and behavioural problems. MST therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behaviour. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. In this updated systematic review and meta-analysis, the authors assessed: (1) impacts of MST on out-of-home placements, crime and delinquency, and other behavioural and psychosocial outcomes for youth and families; (2) consistency of effects across studies; and (3) potential moderators of effects including study location, evaluator independence, and risks of bias. Eligible studies included youth (ages 10 to 17) with social, emotional, and/or behavioural problems who were randomly assigned to licensed MST programmes or other conditions. There were no restrictions on publication status, language, or geographic location. Searches in PsycINFO, MEDLINE, ERIC, NCJRS Abstracts, ProQuest and WorldCAT dissertations and theses and other databases and web sites were performed in 2003, 2010, and March to April 2020. Based on the findings, the authors conclude that the quality of evidence for MST is mixed and effects are inconsistent across studies. Reductions in out-of-home placements and arrest/conviction were observed in the USA, but not in other high-income countries. Studies that compared MST to more active treatments showed fewer benefits, and there is evidence that MST may have had some negative effects on youth outside of the USA. Based on moderate to low quality evidence, MST may reduce self-reported delinquency and improve parent and family outcomes, but there is no overall evidence of effects on youth symptoms, substance abuse, peer relations, or school outcomes.