The chronic nature of chronic myeloid leukemia (CML) has a negative impact on patients’ health-related quality of life (HRQOL) and the need for prolonged oral tyrosine kinase inhibitors (TKIs) poses a risk to low or non-adherence overtime. This systematic review seeks to analyze HRQOL outcomes and adherence to TKIs among pediatric, adolescent and young adult (AYA) patients with CML. Full-text screening ultimately led to the inclusion of 12 articles focused on HRQOL, patient reported outcomes (PRO) and medication adherence. There was heterogeneity in the findings among the included studies, especially in HRQOL and PROs. TKIs adherence ranged from 45-78% using self-report and 58-100% using medical and pharmacy records. Increased TKI adherence was significantly associated with better clinical outcomes, including overall survival. Our findings could inform efforts to develop behavioral interventions to optimize TKI adherence and improve HRQOL outcomes among AYA patients with CML.