Background: Despite adolescent and young adults (AYAs) representing the patient population most likely to initiate and use tobacco and illicit drugs, studies of their impact have thus far focused on older cancer patients or those in survivorship. As sarcomas often serve as a model for AYA care and are associated with poor psychosocial function, frequent delays in diagnosis, and outcomes related to chemotherapy dose density, we sought to understand the impact of tobacco and illicit drug use on diagnosis, chemotherapy delays and dose reductions, and no-show rates in AYAs with sarcoma. Methods: Retrospective chart review was performed on adult AYA patients (18-39 years) with sarcoma seen at least once in 2019 at the University of Wisconsin, identifying documentation of tobacco, marijuana, and other illicit drug use and comparing to pre-identified cancer outcomes including days from symptom onset to tissue diagnosis (with delay defined as > 120 days from symptoms to diagnosis), chemotherapy delays > 1 week and dose reductions, and appointment no-show rates. Current substance use was defined as use following cancer diagnosis. Results: We identified 46 AYAs with sarcoma, with documented tobacco use in 20% as current (9/46), 13% as former (6/46) and 67% as none (31/46). Marijuana and illicit drug use were less frequent at 17% (8/46) and 7% (3/46) respectively. Delayed diagnoses were more common in patients with current tobacco use (6/9, 67%) as compared with former or non-smokers (12/37, 32%, p = 0.12) and were seen in all patients with illicit drug use (3/3, 100%), as compared with only 35% without illicit drug use (15/43, p = 0.05). Of the 24 patients who received chemotherapy, chemotherapy delays and dose reductions were more common in current tobacco users at 86% (6/7) and 29% (2/7) respectively, as compared with patients with former or no tobacco use at 71% (12/17) and 18% (3/17) respectively. Chemotherapy dose reductions were also more common in patients with illicit drug use (2/3, 67%) versus no illicit drug use (3/21, 14%, p = 0.10). Appointment no-show rates were higher in current tobacco users versus former or non-smokers, with 44% (4/9) versus 27% (10/37) with a no-show rate > 5%. In patients with documented substance use, oncology providers documented 93% of tobacco use (14/15) but only 38% marijuana use (3/8) and 33% illicit drug use (1/3) and no oncology providers documented a cessation plan. Conclusions: Current tobacco and illicit drug use in AYAs with sarcoma were associated with delays in diagnosis, increased chemotherapy delays and dose reductions, and higher no-show rates, highlighting modifiable risk factors. Even more strikingly, oncology providers had low rates of documentation of marijuana and illicit drug use in AYAs and no documentation of plans for cessation, highlighting a lost opportunity and the need for more standardized substance use assessment and evidence-based cessation interventions for AYAs with cancer.