Childhood cancer care and outcomes differ widely from country to country due to the inequitable global distribution of medical and surgical resources, sociocultural factors, and biological tumor characteristics. Adapting treatment strategies to the local healthcare system and population is vital to achieve the largest number of children in disease remission, while minimizing the rate of treatment related mortality and complications. By 2050, the total number of new cases of childhood cancer globally is estimated to be 13.7 million, of which 6.1 million (45%) will remain undiagnosed with the current health system disparities. Survival rates for childhood cancer in North America are more than tenfold that in Eastern Africa. Without implementing effective measures to address global barriers to childhood cancer care, there will be approximately 11.1 million preventable deaths in the next 30 years, of which 84% will be in low- and middle-income countries (LMICs). Surgically amenable childhood cancers, such as central nervous system (CNS) tumors, retinoblastoma, and renal tumors, represent a large proportion of the disability-adjusted life years (DALYs) for childhood cancers. Parallel to this, an estimated 1.7 billion children and adolescents do not have access to safe, effective, and timely surgical care. In LMICs, less than 8% of children have access to surgical care, with a critical shortage of surgeons with specialist experience in pediatric cancer surgery. In addition, adjuncts such as chemotherapy, radiotherapy, immunotherapy, and comprehensive multidisciplinary children’s oncology care are often deficient in the LMIC setting. A comprehensive scale-up of interventions is required to address these global inequalities in cancer care, including raising public awareness, offering social support and financial protection to caregivers, improving access to primary care, strengthening referral services, and ensuring the availability of quality care.