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Background The impact of cancer and its treatment on employment and financial burden in adolescents/young adults (AYAs) is not fully known. Methods Eligibility for this cross-sectional study of AYA cancer survivors included the diagnosis of a malignancy between ages 18 and 39 years and survey completion within 1 to 5 years from diagnosis and ≥1 year after therapy completion. Participants were selected randomly from the tumor registries of 7 participating sites and completed an online patient-reported outcomes survey to assess employment and financial concerns. Treatment data were abstracted from medical records. Data were analyzed across diagnoses and by tumor site using logistic regression and Wald-based 95% confidence intervals adjusting for age (categorized), sex, insurance status, education (categorized), and treatment exposures. Results Participants included 872 survivors (breast cancer, n = 241; thyroid cancer, n = 126; leukemia/lymphoma, n = 163; other malignancies, n = 342). Exposure to chemotherapy in breast cancer survivors was associated with an increase in self-reported mental impairment in work tasks (odds ratio [OR], 2.66) and taking unpaid time off (OR, 2.62); survivors of "other" malignancies reported an increase in mental impairment of work tasks (OR, 3.67) and borrowing >$10,000 (OR, 3.43). Radiation exposure was associated with an increase of mental impairment in work tasks (OR, 2.05) in breast cancer survivors, taking extended paid time off work in thyroid cancer survivors (OR, 5.05), and physical impairment in work tasks in survivors of "other" malignancies (OR, 3.11). Finally, in survivors of "other" malignancies, having undergone surgery was associated with an increase in physical (OR, 3.11) and mental impairment (OR, 2.31) of work tasks. Conclusions Cancer treatment has a significant impact on AYA survivors' physical and mental work capacity and time off from work.