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Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Currently, treatment decisions are guided by TNM staging, which omits important negative prognosticators such as lymphovascular invasion, perineural invasion (PNI), and histologic differentiation. We proposed nomogram models based on adverse pathological features to identify candidates suitable for treatment escalation within each risk group according to the National Comprehensive Cancer Network (NCCN) guidelines., Methods: Anonymized clinicopathologic data of OSCC patients from 5 tertiary healthcare institutions in Asia were divided into 3 risk groups according to the NCCN guidelines. Within each risk group, nomograms were built to predict overall survival based on histologic differentiation, histologic margin involvement, depth of invasion (DOI), extranodal extension, PNI, lymphovascular, and bone invasion. Nomograms were internally validated with precision-recall analysis and the Kaplan-Meier survival analysis., Results: Low-risk patients with positive pathological nodal involvement and/or positive PNI should be considered for adjuvant radiotherapy. Intermediate-risk patients with gross bone invasion may benefit from concurrent chemotherapy. High-risk patients with positive margins, high DOI, and a high composite score of histologic differentiation, PNI, and the American Joint Committee on Cancer (AJCC) 8th edition T staging should be considered for treatment escalation to experimental therapies in clinical trials., Conclusion: Nomograms built based on prognostic adverse pathological features can be used within each NCCN risk group to fine-tune treatment decisions for OSCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tu, Shannon, Thankappan, Balasubramanian, Pillai, Shetty, Rangappa, Chandrasekhar, Kekatpure, Kuriakose, Krishnamurthy, Mitra, Pattatheyil, Jain, Iyer, Subramaniam and Iyer.)