In this study, we aimed to develop a novel prognostic algorithm for oral squamous cell carcinoma (OSCC) using a combination of pathogenomics and AI-based techniques. We collected comprehensive clinical, genomic, and pathology data from a cohort of OSCC patients in the TCGA dataset and used machine learning and deep learning algorithms to identify relevant features that are predictive of survival outcomes. Our analyses included 406 OSCC patients. Initial analyses involved gene expression analyses, principal component analyses, gene enrichment analyses, and feature importance analyses. These insights were foundational for subsequent model development. Furthermore, we applied five machine learning/deep learning algorithms (Random Survival Forest, Gradient Boosting Survival Analysis, Cox PH, Fast Survival SVM, and DeepSurv) for survival prediction. Our initial analyses revealed relevant gene expression variations and biological pathways, laying the groundwork for robust feature selection in model building. The results showed that the multimodal model outperformed the unimodal models across all methods, with c-index values of 0.722 for RSF, 0.633 for GBSA, 0.625 for FastSVM, 0.633 for CoxPH, and 0.515 for DeepSurv. When considering only important features, the multimodal model continued to outperform the unimodal models, with c-index values of 0.834 for RSF, 0.747 for GBSA, 0.718 for FastSVM, 0.742 for CoxPH, and 0.635 for DeepSurv. Our results demonstrate the potential of pathogenomics and AI-based techniques in improving the accuracy of prognostic prediction in OSCC, which may ultimately aid in the development of personalized treatment strategies for patients with this devastating disease.