Malnutrition (undernutrition or overweight/obesity) might significantly impact the pharmacokinetics and pharmacodynamics of antineoplastic drugs in children and adolescents (<21 years). A comprehensive systematic literature search was performed on MEDLINE (PubMed), EMBASE, Web of Science, Scopus, ProQuest, Cochrane Trials, and Cochrane Reviews. Databases were searched up to 30 September 2024. Of 4186 articles identified, 150 full texts were evaluated and 12 selected for inclusion. Eight additional articles were identified following a panel review and 6 included, resulting in a total of 18 articles for data extraction. Relevant pharmacokinetic parameters were described for mercaptopurine, vincristine, anthracyclines, methotrexate, busulfan, bevacizumab, and crizotinib. Due to the heterogeneity and limited number of studies per antineoplastic drug, formal statistical analysis or meta-analysis was not appropriate. Variations in the definition of nutritional status, dosing strategies, and type of pharmacokinetic analyses were observed; therefore, no dosing recommendations could be made. With the increasing childhood cancer burden in LMIC, high prevalence of undernutrition, and the global burden of childhood obesity, there is an urgent need for more research in this area. Prospective studies should incorporate uniform definitions and standardised pharmacological approaches to optimise treatment options for children with cancer globally. SYSTEMATIC LITERATURE REVIEW REGISTRATION: PROSPERO: (reference: CRD42023435261).