Background: Adolescent and young adult (AYA) survivors of cancer are at an elevated risk of early-life morbidity and mortality due to the disease trajectory and treatment. Engagement in risk behaviors, including substance use, can exacerbate survivors’ vulnerabilities and place them at further risk for adverse health outcomes. This study provides national estimates of the prevalence of substance use and misuse, substance abuse or dependence (i.e., substance use disorders [SUD]), and receipt of treatment for SUD among AYA cancer survivors. Methods: We used 2015-2018 National Survey of Drug Use and Health data to identify a nationally-representative AYA sample (aged 12-34 years). Outcomes included past-year alcohol use, marijuana use, other illicit drug use, misuse of any prescription psychotherapeutic drugs (including opioid analgesics, stimulants, sedatives, or tranquilizers), and misuse of prescription opioid analgesics. Outcomes also assessed past-year SUD in aforementioned drug classes. Among those with SUD, we evaluated past-year receipt of SUD treatment. Multiple logistic regressions were estimated to compare outcomes between 846 AYAs who reported a cancer history and 142,870 AYAs who did not, adjusting for sociodemographic and need-related characteristics. Results: In bivariate analyses, AYAs with a cancer history were more likely than noncancer peers to use alcohol (78.6% vs. 63.4%; p< 0.001) and illicit drugs other than marijuana (11.2% vs. 7.8%; p= 0.02), misuse any prescription psychotherapeutic drugs (16.9% vs. 10.6%; p< 0.001) and prescription opioid analgesics (12.0% vs. 5.9%; p< 0.001), and have an illicit drug (other than marijuana) SUD (3.7% vs. 1.3%; p< 0.01) in the past year. In regression analyses, differences in past-year misuse of any prescription psychotherapeutic drug and prescription opioid analgesics persisted (p= 0.02, p< 0.01, respectively). Among AYAs with SUD, those with a cancer history were more likely than noncancer peers to receive SUD treatment (21.0% vs. 8.1%; p= 0.01) in the past year; this difference persisted in regression analyses (p= 0.03). Conclusions: AYAs with a cancer history had an elevated risk for misusing prescription psychotherapeutic medications, which was driven by misuse of prescription opioids; yet, only one in five AYAs with a cancer history and SUD received treatment. Our findings underscore the need for future interventions designed to reduce substance use and misuse and improve access to SUD treatment in AYA cancer survivors.