Developed and validated a deep learning radiomics nomogram using multi-phase contrast-enhanced computed tomography (CECT) images to predict neoadjuvant chemotherapy (NAC) response in locally advanced gastric cancer (LAGC) patients.This multi-center study retrospectively included 322 patients diagnosed with gastric cancer from January 2013 to June 2023 at two hospitals. Handcrafted radiomics technique and the EfficientNet V2 neural network were applied to arterial, portal venous, and delayed phase CT images to extract two-dimensional handcrafted and deep learning features. A nomogram model was built by integrating the handcrafted signature, the deep learning signature, with clinical features. Discriminative ability was assessed using the receiver operating characteristics (ROC) curve and the precision-recall (P-R) curve. Model fitting was evaluated using calibration curves, and clinical utility was assessed through decision curve analysis (DCA).The nomogram exhibited excellent performance. The area under the ROC curve (AUC) was 0.848 [95% confidence interval (CI), 0.793-0.893)], 0.802 (95% CI 0.688-0.889), and 0.751 (95% CI 0.652-0.833) for the training, internal validation, and external validation sets, respectively. The AUCs of the P-R curves were 0.838 (95% CI 0.756-0.895), 0.541 (95% CI 0.329-0.740), and 0.556 (95% CI 0.376-0.722) for the corresponding sets. The nomogram outperformed the clinical model and handcrafted signature across all sets (all P < 0.05). The nomogram model demonstrated good calibration and provided greater net benefit within the relevant threshold range compared to other models.This study created a deep learning nomogram using CECT images and clinical data to predict NAC response in LAGC patients undergoing surgical resection, offering personalized treatment insights.© 2024. The Author(s).