Background: Fatigue is one of the most important quality of life issues experienced by patients being treated with oral targeted therapy for chronic myeloid leukemia (CML). However, no intervention exists that specifically addresses strategies to reduce targeted therapy-related fatigue. Objective: This study adapted an evidence-based clinic-delivered intervention (EBI) "cognitive behavior therapy for post-cancer fatigue" for use in CML patients. The existing EBI was based on 6 established perpetuating factors of fatigue (ie, sleep, activity, helpful thinking, coping with cancer, social support, and fear of disease recurrence). Study aims were to gauge reactions to (1) existing content and (2) a new Internet-assisted intervention delivery format. Methods: Guided by the ADAPT-ITT framework, we used a series of systematic steps and adaptation methodologies, including semistructured interviews with CML patients and providers and feedback from topical experts. Results: Patients were receptive to existing content topics and an Internet-assisted delivery format was acceptable. A key theme reflected the need for a new customized psychoeducational module about CML as a disease and its treatment. Both providers and patients held positive views about the potential of the adapted EBI to improve fatigue. Conclusions: Findings offered essential guidance for the adaptation and reinforced the utility of the adapted intervention. Implications for Practice: Adapting existing EBIs for new audiences contributes to advancing findings of evidence-based research, ultimately providing nurses and other healthcare providers with important referral options to interventions that may provide useful strategies to improve quality of life and reduce targeted therapy-related fatigue.