Although metabolic intratumoral heterogeneity (ITH) gives important value on treatment responses and prognoses, its association with treatment outcomes have not been reported in gastric cancer (GC). We aimed to evaluate temporal changes in metabolic ITH and the associations with treatment responses, progression-free survival (PFS), and overall survival (OS) in advanced GC patients. Eighty-five patients with unresectable, locally advanced, or metastatic GC were prospectively enrolled before the first-line palliative chemotherapy and underwent [F]FDG PET at baseline (TP1) and the first response follow-up evaluation (TP2). Standardized uptake values (SUVs), volumetric parameters, and textural features were evaluated in primary gastric tumor at TP1 and TP2. Of 85 patients, 44 had partial response, 33 had stable disease, and 8 progressed. From TP1 to TP2, metabolic ITH was significantly reduced (P < 0.01), and the degree of the decrease was greater in responders than in non-responders (P < 0.01). Using multiple Cox regression analyses, a low SUV at TP2, a high kurtosis at TP2 and larger decreases in the coefficient of variance were associated with better PFS. A low SUV at TP2, larger decreases in the metabolic tumor volume and larger decreased in the energy were associated with better OS. Age older than 60 years and responders also showed better OS. An early reduction in metabolic ITH is useful to predict treatment outcomes in advanced GC patients.