Purpose of Review <p>Cancer-related fatigue (CRF) is a prevalent and debilitating symptom among breast cancer survivors​ with a significant adverse impact on quality of life​. This comprehensive review synthesizes the current understanding of CRF’s complex pathophysiology, including the interplay of inflammatory, neuroendocrine, and psychosocial mechanisms​, and evaluates diverse intervention strategies.</p> Recent Findings <p>Non-pharmacologic approaches (e.g., structured exercise, cognitive-behavioural therapy, mindfulness) have the strongest evidence for alleviating CRF and are emphasized as first-line treatments in oncology guidelines (e.g., ASCO, NCCN, ESMO). In contrast, pharmacologic options such as psychostimulants or bupropion show only modest benefits​, with mixed efficacy and notable side effects​, underscoring their limited role. Comparing oncology-focused guidelines with those for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) which are psychiatry-focused highlight key differences in management approaches and the need for a unified, multidisciplinary framework across specialties.</p> Summary <p>Modern multidisciplinary, individualized survivorship care, integrating oncologic, psychosocial, and rehabilitative strategies call for adoption of updated, integrated clinical guidelines to optimally address CRF​. By consolidating evidence and expert recommendations, this review aims to inform and enhance the clinical management of CRF and improve survivorship outcomes for breast cancer survivors.</p>