Oral cancer (OC) is one of the most commonly diagnosed head and neck cancers and includes malignancies arising from the tongue, lips, floor of the mouth, buccal mucosa, hard palate, alveolar ridge, gingiva, and oropharynx. The most common histological type is squamous cell carcinoma, which originates from squamous cells lining the mouth and throat and accounts for over 90% of all OC cases. Notably, OC, with a five-year survival rate of approximately 68% represents a significant health burden worldwide. Biomarkers are used as molecular signatures, enabling the objective differentiation between normal and pathological conditions as well as quantifiable characteristics of disease processes, pharmacological responses to therapeutic interventions, prediction of clinically relevant endpoints, and development of personalized therapies. In the intricate landscape of OC progression, inflammation within the tumor microenvironment emerges as a central player. Predictive biomarkers include tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17, and interferon-gamma (IFN-γ), which modulate tumor growth and affect response to cancer therapy. Prognostic biomarkers, such as IL-6, IL-8, IL-1α, IL-1β, cyclooxygenase (COX)-2, C-reactive protein (CRP), and hematological parameters, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and monocyte-to- lymphocyte ratio provide insights into clinical outcomes. Diagnostic biomarkers, such as IL-1β, IL-8, TNF-α, and COX-2, assist in predicting carcinogenesis or determining cancer subtypes. Monitoring biomarkers, including salivary cytokines (IL-1β, IL-8, and IL-6) and TNF-α, help evaluate changes in disease status. Overall, emerging data suggest that biomarkers of inflammation provide invaluable tools for the evaluation of cancer progression, prognosis, and clinical outcomes.