BACKGROUND: This study aimed to develop a multi-modality model by incorporating pretreatment computed tomography (CT) radiomics and pathomics features along with clinical variables to predict pathologic complete response (pCR) to neoadjuvant chemoimmunotherapy in patients with locally advanced esophageal cancer (EC). METHOD: A total of 223 EC patients who underwent neoadjuvant chemoimmunotherapy followed by surgical intervention between August 2021 and December 2023 were included in this study. Radiomics features were extracted from contrast-enhanced CT images using PyrRadiomics, while pathomics features were derived from whole-slide images (WSIs) of pathological specimens using a fine-tuned deep learning model (ResNet-50). After feature selection, three single-modality prediction models and a combined multi-modality model integrating two radiomics features, 11 pathomics features, and two clinicopathological features were constructed using the support vector machine (SVM) algorithm. The performance of the models were evaluated using receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA). Shapley values were also utilized to explain the prediction model. RESULTS: The predictive capability of the multi-modality model in predicting pCR yielded an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.75-1.00), outperforming the radiomics model (AUC 0.70 [95% CI 0.54-0.85]), pathomics model (AUC 0.77 [95% CI 0.53-1.00]), and clinical model (AUC 0.63 [95% CI 0.46-0.80]). Additionally, both the calibration plot and DCA curves support the clinical utility of the integrated multi-modality model. CONCLUSIONS: The combined multi-modality model we propose can better predict the pCR status of esophageal cancer and help inform clinical treatment decisions.