Purpose <p>Cancer-related fatigue (CRF) can be a persistent and severe consequence of cancer treatment. Cognitive behavioral therapy for insomnia (CBT-I) can improve CRF in those with insomnia comorbid with cancer. This secondary analysis of a randomized controlled trial investigated what proportion of participants benefit and the factors associated with an improvement in CRF following CBT-I.</p> Methods <p>Atlantic Canadian cancer survivors (<i>N</i> = 121) with insomnia disorder and perceived cognitive impairment symptoms were recruited to participate in a randomized controlled trial of CBT-I. Fatigue was measured using the Multidimensional Fatigue Symptom Inventory–Short Form. Univariable and multivariable binary logistic regressions were used to assess clinical, symptom, and demographic factors associated with a significant improvement in CRF after CBT-I.</p> Results <p>The majority (75%) of the sample (<i>M</i>_age = 60.12&#xa0;years, 77% women, 45% breast cancer) experienced a significant reduction in CRF symptoms following the intervention. Being younger (under 55), being female, having anxiety, and undergoing chemotherapy were associated with a greater likelihood of improvement in CRF at the univariable level. At the multivariable level, only younger age was significantly associated with an improvement in CRF after CBT-I.</p> Conclusion <p>CBT-I can effectively reduce CRF in cancer survivors who also experience insomnia. Differences in sleep patterns and/or the number of comorbid physical health concerns between younger and older people may explain why CBT-I improved CRF more in younger participants. Future research is needed to better understand the demographic, symptom, and clinical variables that may influence treatment response.</p> Trial registration <p>This is a secondary analysis of a registered randomized controlled trial (clinicaltrials.gov identifier: NCT04026048).</p>