Child trafficking and exploitation remain significant public health challenges and human rights violations in the United States (US), where it mainly impacts youth in foster care, unstable housing, and other marginalized communities. Multi-agency and collective responses are needed to prevent, identify, and respond to exploitation, but evidence on interventions is fragmented across sectors. For this scoping review, only studies based in the United States were considered regarding multi-agency response to child trafficking and exploitation. Data were extracted and synthesized systematically to explore legislative frameworks, risk factors, collaborative practice, and outcomes. In the US, responses to child trafficking and exploitation are based on extensive federal and state legislation that requires multi-agency approaches from criminal justice, child welfare, health care, education, and community systems; however, implementation and integration across these systems vary considerably. Across studies, risk of trafficking was characterized by intersections of structural, familial, and individual vulnerabilities, with the highest risks in youth experiencing homelessness and LGBTQ+ youth. Common channels of exploitation were through facilitation by a family member, romantic or peer recruitment, and increasingly through online pathways, reinforced by dependency, traumatic bonding, and barriers to exit. Multi-agency collaboration, integrated health and social services, trauma-informed and survivor-centered practices, were associated with improved identification, engagement, and recovery outcomes. However, most collaborations lacked formal infrastructure, sustainable funding, standardized screening methods, consistent training, and evaluation mechanisms, limiting effectiveness and scalability. Together, trauma-informed and survivor-centered multi-agency systems are essential to addressing child trafficking and exploitation beyond enforcement-focused responses. Strengthening formal collaboration structures and addressing underlying structural vulnerabilities are critical for sustained prevention and recovery.