In Central America, childhood cancer is one of the leading causes of death. It is also a significant disease burden to health systems, with social and economic implications for families. The World Health Organization (WHO), the Executive Secretary of the Council of Ministers of Health of Central America and the Dominican Republic (SE-COMISCA), the Pan American Health Organization (PAHO), and St Jude Children’s Research Hospital are working collaboratively to strengthen the health system’s response to childhood cancer in Central America and the Dominican Republic. This collaboration’s primary objective is to support the development of national pediatric cancer plans for each country in the subregion and improve overall survival rates and quality of care for children with cancer through a more comprehensive universal health coverage package. This collaborative effort has led to: (i) the development of childhood cancer national action plans; (ii) the launch of awareness and promotion campaigns; (iii) the design of childhood cancer educational material for children and their families; and (iv) a platform for professionals working in childhood cancer to share good practices and successful experiences. The countries of the subregion together with PAHO and St Jude Children’s Research Hospital are working to develop standardized evidence-based clinical practice guidelines on childhood cancer for the region. This brief communication reports on this collaborative work.