PURPOSE: We sought to develop and validate machine learning (ML) models for predicting tumor grade and prognosis using 2-[F]fluoro-2-deoxy-D-glucose ([F]FDG) positron emission tomography (PET)-based radiomics and clinical features in patients with pancreatic neuroendocrine tumors (PNETs). PROCEDURES: A total of 58 patients with PNETs who underwent pretherapeutic [F]FDG PET/computed tomography (CT) were retrospectively enrolled. PET-based radiomics extracted from segmented tumor and clinical features were selected to develop prediction models by the least absolute shrinkage and selection operator feature selection method. The predictive performances of ML models using neural network (NN) and random forest algorithms were compared by the areas under the receiver operating characteristic curves (AUROCs) and validated by stratified five-fold cross validation. RESULTS: We developed two separate ML models for predicting high-grade tumors (Grade 3) and tumors with poor prognosis (disease progression within two years). The integrated models consisting of clinical and radiomic features with NN algorithm showed the best performances than the other models (stand-alone clinical or radiomics models). The performance metrics of the integrated model by NN algorithm were AUROC of 0.864 in the tumor grade prediction model and AUROC of 0.830 in the prognosis prediction model. In addition, AUROC of the integrated clinico-radiomics model with NN was significantly higher than that of tumor maximum standardized uptake model in predicting prognosis (P < 0.001). CONCLUSIONS: Integration of clinical features and [F]FDG PET-based radiomics using ML algorithms improved the prediction of high-grade PNET and poor prognosis in a non-invasive manner.