Abstract <p>Despite potential benefits, the clinical uptake of precision-guided treatment (PGT) in paediatric oncology remains low. This systematic review aimed to identify factors affecting the adoption of PGT recommendations for children with cancer. Five databases (EMBASE, CINAHL, PubMed, PsycINFO, Scopus) were systematically searched. Qualitative and quantitative studies involving patients aged 0–21 years were included. Two reviewers conducted screening and data extraction. Seventeen studies, all from developed countries, met the criteria: 10 prospective, 4 retrospective, and 3 cross-sectional, involving 3976 patients, 227 healthcare professionals, 189 parents, and 532 community members. Most studies were quantitative, collating factors from clinical records; two qualitative studies used interviews to explore clinician and parent perspectives. Three key domains of factors were identified: (i) decision maker-related characteristics; (ii) decision-specific criteria; and (iii) contextual factors. Common factors included limited drug/clinical trial access, ongoing alternative treatments, high costs, and patient or family preferences. These interlinked factors may affect uptake individually and collectively. To our knowledge, this is the first review to map factors influencing the implementation of PGT in paediatric cancer. Further research is needed to clarify the relative importance of these factors and to better understand oncologists’ perspectives when making recommendations in partnership with patients and families.</p> Registration <p>PROSPERO database (CRD42023410199)</p>