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Multisystem-involved youth are children and adolescents concurrently served in the child welfare, behavioral health, and/or juvenile justice systems. These youth are a high risk and vulnerable population, often due to their experience of multiple adversities and trauma, yet little is known about their multiple needs and pathways into multisystem involvement. Multisystem-involved youth present unique challenges to researchers, practitioners, and policymakers. In this article, we summarize the literature on multisystem-involved youth, including prevalence, characteristics, risk factors, and disparities for this population. We then describe a developmental cascade framework, which specifies how exposure to adverse experiences in childhood may have a “cascading” or spillover effect later in development, to depict pathways of multisystem involvement and opportunities for intervention. This framework offers a multidimensional view of involvement across service systems and illustrates the complexities of relationships between micro- and macro-level factors at various stages and domains of development. We conclude that multisystem-involved youth are an understudied population that may represent majority of youth who are already served in another service system. Many of these youth are also disproportionately from racial and ethnic minority backgrounds. Currently, for multisystem-involved youth and their families, there is a lack of standardized and integrated screening procedures to identify youth with open cases across service systems; inadequate use of available instruments to assess exposure to complex trauma; inadequate clinical and family-related evidence-based practices specifically for use with this population; and poor cross-systems collaboration and coordination that align goals and targeted outcomes across systems. We make recommendations for research, practice, and systems development to address the needs of multisystem-involved youth and their families.