Objective: This study aimed to predict therapeutic efficacy among diffuse large B-cell lymphoma (DLBCL) after R-CHOP (-like) therapy using baseline F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG PET) radiomics. Methods: A total of 239 patients with DLBCL were enrolled in this study, with 82 patients having refractory/relapsed disease. The radiomics signatures were developed using a stacking ensemble approach. The efficacy of the radiomics signatures, the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), conventional PET parameters model, and their combinations in assessing refractory/relapse risk were evaluated using receiver operating characteristic (ROC) curves, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and decision curve analysis. Results: The stacking model, along with the integrated model that combines stacking with the NCCN-IPI and SDmax (the distance between the two lesions farthest apart, normalized to the patient's body surface area), showed remarkable predictive capabilities with a high area under the curve (AUC), sensitivity, specificity, PPV, NPV, accuracy, and significant net benefit of the AUC (NB-AUC). Although no significant differences were observed between the combined and stacking models in terms of the AUC in either the training cohort (AUC: 0.992 vs. 0.985, p = 0.139) or the testing cohort (AUC: 0.768 vs. 0.781, p = 0.668), the integrated model exhibited higher values for sensitivity, PPV, NPV, accuracy, and NB-AUC than the stacking model. Conclusion: Baseline PET radiomics could predict therapeutic efficacy in DLBCL after R-CHOP (-like) therapy, with improved predictive performance when incorporating clinical features and SDmax.