The objective of our study is to investigate the predictive value of various combinations of radiomic features from intratumoral and different peritumoral regions of interest (ROIs) for achieving a good pathological response (pGR) following neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). This retrospective study was conducted using data from LARC patients who underwent nCRT between 2013 and 2021. Patients were divided into training and validation cohorts at a ratio of 4:1. Intratumoral ROIs (ROIITU) were segmented on T2–weighted imaging, while peritumoral ROIs were segmented using two methods: ROIPTU_2mm, ROIPTU_4mm, and ROIPTU_6mm, obtained by dilating the boundary of ROIITUby 2 mm, 4 mm, and 6 mm, respectively; and ROIMR_Fand ROIMR_BVLN, obtained by separating the fat and blood vessels + lymph nodes in the mesorectum. After feature extraction and selection, 12 logistic regression models were established using radiomics features derived from different ROIs or ROI combinations, and five–fold cross–validation was performed. The average area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the models. The study included 209 patients, consisting of 118 pGR and 91 non–pGR patients. The model that integrated ROIITUand ROIMR_BVLNfeatures demonstrated the highest predictive ability, with an AUC (95% confidence interval) of 0.936 (0.904–0.972) in the training cohort and 0.859 (0.745–0.974) in the validation cohort. This model outperformed models that utilized ROIITUalone (AUC = 0.779), ROIMR_BVLNalone (AUC = 0.758), and other models. The radscore derived from the optimal model can predict the treatment response and prognosis after nCRT. Our findings validated that the integration of intratumoral and peritumoral radiomic features, especially those associated with mesorectal blood vessels and lymph nodes, serves as a potent predictor of pGR to nCRT in patients with LARC. Pending further corroboration in future research, these insights could provide novel imaging markers for refining therapeutic strategies.