Description: The tumor proliferation marker, Ki-67 index, is a well-established prognostic marker in gastroenteropancreatic neuroendocrine neoplasms (NENs). Noninvasive molecular imaging allows whole-body metabolic characterization of metastatic disease. We investigated the prognostic impact of 18 F-FDG PET in inoperable multifocal disease. Methods: Retrospective, dual-center analysis was performed on 89 patients with histologically confirmed, inoperable metastatic gastroenteropancreatic NENs undergoing 18 F-FDG PET/CT within the staging routine. Metabolic (PET-based) grading was in accordance with the most prominent 18 F-FDG uptake (reference tumor lesion): mG1, tumor-to-liver ratio of maximum standardized uptake value ≤ 1.0; mG2, 1.0–2.3; mG3, 〉2.3. Other potential variables influencing overall survival, including age, tumor origin, performance status, tumor burden, plasma chromogranin A (≥600 μg/L), neuron-specific enolase (≥25 μg/L), and classic grading (Ki-67–based) underwent univariate (log-rank test) and multivariate analysis (Cox proportional hazards model), with a P value of less than 0.05 considered significant. Results: The median follow-up period was 38 mo (95% confidence interval [CI], 27–49 mo); median overall survival of the 89 patients left for multivariate analysis was 29 mo (95% CI, 21–37 mo). According to metabolic grading, 9 patients (10.2%) had mG1 tumors, 22 (25.0%) mG2, and 57 (64.8%) mG3. On multivariate analysis, markedly elevated plasma neuron-specific enolase ( P = 0.016; hazard ratio, 2.9; 95% CI, 1.2–7.0) and high metabolic grade ( P = 0.015; hazard ratio, 4.7; 95% CI, 1.2–7.0) were independent predictors of survival. Conclusion: This study demonstrated the feasibility of prognostic 3-grade stratification of metastatic gastroenteropancreatic NENs by whole-body molecular imaging using 18 F-FDG PET.