Cancer-related fatigue (CRF) is a common and distressing side effect of cancer and its treatment, often persisting for years after treatment completion. The prevalence and impact of CRF on quality of life are significant, and it may be a risk factor for reduced survival. Inflammation has emerged as a key biological pathway contributing to CRF, with studies linking inflammatory markers to fatigue before, during, and after treatment. Longitudinal studies have identified genetic, biological, psychosocial, and behavioral risk factors for CRF, including pre-treatment fatigue, depression, sleep disturbance, physical inactivity, and elevated body mass index. Various intervention approaches, such as physical activity, psychosocial, mind-body, and pharmacological treatments, have been evaluated in randomized controlled trials. While there is no single "gold standard" treatment, several interventions have shown beneficial effects, particularly in reducing fatigue during and after treatment. Physical activity, especially aerobic exercise, has been found to be effective, with meta-analyses showing moderate to large effect sizes. Psychosocial interventions, such as cognitive-behavioral therapy and psychoeducation, have also demonstrated beneficial effects. Mind-body approaches like mindfulness meditation, yoga, and acupuncture show promise, though more research is needed. Pharmacological treatments, including hematopoietic growth factors and psychostimulants, have shown varying degrees of effectiveness. Overall, the multifactorial nature of CRF requires a comprehensive approach to management, and future research should focus on identifying and targeting specific risk factors and interventions for different stages of the cancer trajectory.Cancer-related fatigue (CRF) is a common and distressing side effect of cancer and its treatment, often persisting for years after treatment completion. The prevalence and impact of CRF on quality of life are significant, and it may be a risk factor for reduced survival. Inflammation has emerged as a key biological pathway contributing to CRF, with studies linking inflammatory markers to fatigue before, during, and after treatment. Longitudinal studies have identified genetic, biological, psychosocial, and behavioral risk factors for CRF, including pre-treatment fatigue, depression, sleep disturbance, physical inactivity, and elevated body mass index. Various intervention approaches, such as physical activity, psychosocial, mind-body, and pharmacological treatments, have been evaluated in randomized controlled trials. While there is no single "gold standard" treatment, several interventions have shown beneficial effects, particularly in reducing fatigue during and after treatment. Physical activity, especially aerobic exercise, has been found to be effective, with meta-analyses showing moderate to large effect sizes. Psychosocial interventions, such as cognitive-behavioral therapy and psychoeducation, have also demonstrated beneficial effects. Mind-body approaches like mindfulness meditation, yoga, and acupuncture show promise, though more research is needed. Pharmacological treatments, including hematopoietic growth factors and psychostimulants, have shown varying degrees of effectiveness. Overall, the multifactorial nature of CRF requires a comprehensive approach to management, and future research should focus on identifying and targeting specific risk factors and interventions for different stages of the cancer trajectory.