<strong>Background:</strong> Many childhood cancers are treatable with cure rates between 70% and 80% in well-resourced countries, while approximately 80% of African children with cancer die without access to adequate care. South Africa has an established oncology health care service with overburdened infrastructure, low cancer awareness in the primary health care service and widespread service delivery challenges.<br /><strong>Aim:</strong> The aim of this study was to explore, document and analyse the subjective experience of childhood cancer-related challenges in South Africa, and to make the results available to stakeholders.<br /><strong>Setting:</strong> A total of 58 patient-participants (childhood cancer patients, parents and guardians of children with cancer) and 10 paediatric oncology workers (oncology social workers, oncology nurses and interim home carers) were selected from tertiary oncology centres and from the Childhood Cancer Foundation of South Africa (CHOC) interim care homes across South Africa.<br /><strong>Method:</strong> Participants were selected via convenience sampling and qualitative data were derived from face-to-face photovoice interviews conducted by psychologists and social workers and supported by translators when necessary.<br /><strong>Results:</strong> Nine themes of cancer challenges were identified via thematic content analysis of the photo-narratives, that is, physical and treatment challenges, emotional, poor services, transport, finances, information, powerlessness, stigma and schooling challenges.<br /><strong>Conclusion:</strong> Lack of awareness and knowledge about cancer at the African traditional healer, primary and regional health care service levels were frequent challenges. Important feedback included lack of patient-centred care, separation of children with cancer from guardians, diagnostic delays, permanent disabilities for children because of cancer, emotional trauma, special needs of teenagers and a lack of community and palliative care support.