BACKGROUND: Symptom management for infants, children and young people at end of life is complex and challenging due to the range of conditions and differing care needs of individuals of different ages. A greater understanding of these challenges could inform the development of effective interventions. AIM: To investigate the barriers and facilitators experienced by patients, carers and healthcare professionals managing symptoms in infants, children and young people at end of life. DESIGN: A mixed-methods systematic review and meta-analysis was undertaken (PROSPERO ID: CRD42019124797). DATA SOURCES: The Cochrane Library, PROSPERO, CINAHL, MEDLINE, PsycINFO, Web of Science Core Collection, ProQuest Dissertations & Theses Database, Evidence Search and OpenGrey were electronically searched from the inception of each database for qualitative, quantitative or mixed-methods studies that included data from patients, carers or healthcare professionals referring to barriers or facilitators to paediatric end-of-life symptom management. Studies underwent data extraction, quality appraisal, narrative thematic synthesis and meta-analysis. RESULTS: A total of 64 studies were included (32 quantitative, 18 qualitative and 14 mixed-methods) of medium-low quality. Themes were generated encompassing barriers/facilitators experienced by carers (treatment efficacy, treatment side effects, healthcare professionals' attitudes, hospice care, home care, families' symptom management strategies) and healthcare professionals (medicine access, treatment efficacy, healthcare professionals' demographics, treatment side effects, specialist support, healthcare professionals' training, health services delivery, home care). Only one study included patients' views. CONCLUSION: There is a need for effective communication between healthcare professionals and families, more training for healthcare professionals, improved symptom management planning including anticipatory prescribing, and urgent attention paid to the patients' perspective.