The oral cavity hosts over 800 bacterial species, including key pathogens linked to periodontal disease like Streptococcus mutans and Porphyromonas gingivalis. This discussion examines how microbial infections and inflammation pathways contribute to cancer development. Pathogens disrupt immune responses and cause DNA methylation changes, associated with bacteria such as H. pylori and F. nucleatum. Periodontal disease-related inflammation connects to cancer through infection, inflammatory mediators, and risk factors. These pathogens independently increase oral squamous cell carcinoma risk in non-smokers and HPV-negative individuals, showing microbiome-induced inflammation’s role in cancer. Disruption of the gingival barrier leads to inflammation and potential cancer, with epigenetic changes in periodontal tissues highlighting how infections and inflammation drive disease and cancer risk.