PURPOSE: The majority of children, adolescents, and young adults treated with neurotoxic chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN). This side effect can cause numbness and tingling, distal weakness, and autonomic symptoms. These symptoms can lead to impaired physical function and interrupt the development of a child's motor skills. This systematic review provides an essential overview of the relationship between CIPN and physical function impairments, activity limitations, and participation restrictions in children, adolescents, and young adults with cancer. METHODS: Following PRISMA guidelines, a search was conducted using the MEDLINE and CINAHL databases between 2013 and March 2024. The quality of each study was assessed using the Joanna Briggs Critical Appraisal Tools. A total of 14 studies were included. RESULTS: This critical review demonstrated significant relationships between CIPN and measures of manual dexterity, gait, balance, motor proficiency, and health-related quality of life. These relationships were observed during treatment and persisted in many survivors years after completing treatment. Higher-level skills such as running speed, standing on one leg, and gait quality over time were more likely to be impacted than basic mobility. CONCLUSION: CIPN impacts multiple components of physical function and health-related quality of life in survivors of pediatric cancer. In addition to pharmacological and non-pharmacological interventions targeted at these limitations, greater understanding is needed regarding the longitudinal course of these findings with comprehensive assessments sensitive to higher-level physical function. IMPLICATIONS FOR CANCER SURVIVORS: Assessment of CIPN and physical function for survivors treated with neurotoxic agents is critical to guiding supportive care interventions aimed at improving cancer survivorship.