BACKGROUND: We aimed to develop a machine learning model based on intratumoral and peritumoral METHODS: This retrospective study included 296 NSCLC patients, including a training cohort (N = 183), a testing cohort (N = 78), and a TCIA radiogenomic cohort (N = 35). The extreme gradient boosting algorithm was employed to develop the radiomic models. RESULTS: The COMB-Radscore, which was developed by combining radiomic features from PET, CT, and PET/CT images, had the most satisfactory predictive performance with AUC (ROC) 0.894 and 0.819 in the training and testing cohorts, respectively. Survival analysis has demonstrated that COMB-Radscore is an independent prognostic factor for progression-free survival and overall survival. Moreover, COMB-Radscore demonstrates excellent dynamic predictive performance, with an AUC (ROC) of 0.857, enabling the earlier detection of potential disease progression in patients compared to radiological evaluation solely relying on tumor size. Further radiogenomic analysis showed that the COMB-Radscore was associated with infiltration abundance and functional status of CD8 + T cells. CONCLUSIONS: The radiomic model holds promise as a precise, personalized, and dynamic decision support tool for the treatment of NSCLC patients.