PURPOSE The purpose of this report, commissioned by Teen Cancer America and performed by Deloitte Access Economics in 2021, was to estimate the total costs incurred by adolescent and young adults (AYAs) after cancer diagnosis in the United States (US) over their life course. METHODS The incidence of cancer in 2019 among AYAs age 15-39 years was estimated from the US Cancer Statistics Public Use Database, and relative survival was projected from the Surveillance, Epidemiology, and End Results Program. Cost domains included health system, productivity, and well-being costs. Components were estimated with published literature and pooled data from the Medical Expenditure Panel Survey from 2008 to 2012 and inflated to 2019 dollars. RESULTS The economic and human costs of cancer in AYAs are substantial—$23.5 billion overall, corresponding to $259,324 per person over the lifetime. The majority of costs are borne by AYA cancer survivors themselves in the form of lost productivity, loss of well-being, and loss of life. CONCLUSION These findings underscore the need to address the burden of cancer in AYAs through targeted programs for AYAs, such as financial navigation and health insurance literacy interventions, as well as local and national policy initiatives to address access to and enhanced coverage for clinical trials participation, fertility services, and survivorship care.