Purpose <p>To assess the prevalence and severity of cancer-related fatigue (CRF) in patients with advanced gastric cancer and its association with clinicopathological and psychosocial factors, including anxiety and depression.</p> Method <p>In a prospective cohort study, 97 patients with advanced gastric cancer on chemotherapy were prospectively assessed using the Brief Fatigue Inventory (BFI), FACT-G for quality of life, HAM-A for anxiety, and HAM-D for depression. Statistical analyses evaluated associations and predictors, with survival compared by fatigue severity.</p> Results <p>Severe fatigue was present in 32% of patients, associated significantly with female gender (<i>p</i> = 0.009), comorbidity (<i>p</i> = 0.02), severe anxiety (<i>p</i> &lt; 0.0001), and severe depression (<i>p</i> &lt; 0.0001), but not with age or most clinical variables. Quality of life was moderately reduced, particularly in functional well-being. Patients with mild fatigue had longer median survival (19 vs. 11 months; <i>p</i> = 0.028). Fatigue severity independently predicted survival (HR = 0.597, <i>p</i> = 0.033).</p> Conclusion <p>CRF is common in advanced gastric cancer and strongly linked to psychological distress and comorbidity. Severe fatigue correlates with lower quality of life and shorter survival, indicating the need for targeted strategies addressing both fatigue and mental health.</p>