Advances in the diagnosis and management of childhood cancers have significantly improved survival, and 80% of those who have access to contemporary treatment are expected to survive into adulthood. Multimodality protocols incorporating high-intensity cytotoxic chemotherapy and radiotherapy may be associated with increased acute and delayed adverse effects, thereby compromising the quality of life. Furthermore, curative therapeutic options remain limited in the context of metastatic, relapsed or refractory disease as well as rare tumour entities. This has prompted a paradigm shift in pediatric oncology care in the contemporary era, encompassing multiple domains including cancer predisposition, immunotherapy, precision medicine and survivorship, aimed at optimising survival while minimising treatment-related toxicity and improving quality of life. While these advances are increasingly evident in high-income countries, several hurdles and challenges exist in the implementation of these strategies in low-income and middle-income countries (LMICs). Key barriers include restricted accessibility and affordability of newer and advanced diagnostic modalities and therapeutic agents, deficient infrastructure, non-availability of targeted agents and newer immunotherapy drugs, logistical and regulatory hurdles, limited access to clinical trials and inadequate long-term follow-up. Substantial changes are requisite to facilitate the translation of these changing paradigms into reality in India and LMICs.