Background: Pancreas NETs are uncommon and very rare cancer accounting for around 7% of the pancreatic cancer sub patient population, 4,200 patients in the US diagnoses yearly of all cancers in the pancreas. There are very few treatment options available for Metastatic Pancreatic Neuroendocrine Tumor patients. The survival rate depends on a variety of factors, including whether the tumor can be removed using surgery and if the cancer has spread to other parts of the body. The 5-year survival rate non-metastatic pancreas NETs is 93% while metastatic pancreas NETs is 24%. Therefore, this study compares the 5-year overall survival rate of metastatic pancreatic NETs ineligible for surgery who have received chemotherapy alone versus who have received targeted therapy. Methods: Patient cohorts were generated in an electronic medical records (EMR) TriNetX Research Network of 89M patient lives. Patients were identified as either receiving a targeted therapy or patients who were targeted therapy naïve receiving chemotherapy. Both cohorts had a diagnosis of pancreatic NETs (ICD-10 C25.4), at least one documentation of a related metastasis, and no history of any pancreatic surgery. The 5 year overall survival (OS) from first exposure to either targeted therapy or chemotherapy was analyzed using measures of association and survival analysis conducted via Kaplan-Meier estimator. Cohort comparisons were with propensity score matching (PSM) to control for demographic, comorbidity, medication, and diagnostic procedure confounders. Results: After matching, each cohort accounted for 389 patients (43% female, mean age at index 62 +/- 13 SD). There was a significant 5-year mortality risk difference (11.054%, p = 0.0020) between the chemotherapy only cohort (215 patients, 55.27%) vs. the targeted therapy cohort (172 patients, 44.216%) after adjusting for potential confounding factors. Additionally, the 5-year OS rate was 24.951% in the chemotherapy only cohort and 37.222% in the targeted therapy cohort. The difference in survival between the groups was statistically significant (log-rank p = 0.0001). Conclusions: In these cohorts of patients with metastatic pancreas NETs without surgical treatment, we found that targeted therapy was associated with a significant improvement in 5-year overall survival compared to standard chemotherapy alone. Our results suggest that targeted therapy should be considered as a first line treatment option for this severe patient population.