Abstract Background Cancer and its treatment can result in lifelong medical financial hardship, which we aimed to describe among adult survivors of adolescent and young adult (AYA) cancers in the United States. Methods We identified adult (aged ≥18 years) survivors of AYA cancers (diagnosed ages 15-39 years) and adults without a cancer history from the 2010-2018 National Health Interview Surveys. Proportions of respondents reporting measures in different hardship domains (material [eg, problems paying bills], psychological [eg, distress], and behavioral [eg, forgoing care due to cost]) were compared between groups using multivariable logistic regression models and hardship intensity (cooccurrence of hardship domains) using ordinal logistic regression. Cost-related changes in prescription medication use were assessed separately. Results A total of 2588 AYA cancer survivors (median = 31 [interquartile range = 26-35] years at diagnosis; 75.0% more than 6 years and 50.0% more than 16 years since diagnosis) and 256 964 adults without a cancer history were identified. Survivors were more likely to report at least 1 hardship measure in material (36.7% vs 27.7%, P < .001) and behavioral (28.4% vs 21.2%, P < .001) domains, hardship in all 3 domains (13.1% vs 8.7%, P < .001), and at least 1 cost-related prescription medication nonadherence (13.7% vs 10.3%, P = .001) behavior. Conclusions Adult survivors of AYA cancers are more likely to experience medical financial hardship across multiple domains compared with adults without a cancer history. Health-care providers must recognize this inequity and its impact on survivors’ health, and multifaceted interventions are necessary to address underlying causes.