Oral squamous cell carcinoma (OSCC) is the most common oral cavity malignancy associated with multiple risk factors. In the last 14 years, oral dysbiosis has attracted the scientific community’s attention as a potential oncogenic factor, in parallel with the development of omics technologies that have revolutionized microbiological research. The present umbrella review aimed to investigate the oral microbiological content (bacilli, viruses, and fungi) of tissue and saliva samples from adult (>18 years) patients with OSCC. The secondary objective was to compare the oral microbiome of OSCC subjects with non-OSCC subjects. The study protocol was under the PRISMA statement and registered on PROSPERO (CRD42023448153). Data from 32 systematic reviews were extracted, qualitatively summarized, and analyzed using AMSTAR-2. An increase in oral bacteria of the phylum Fusobacteria, Proteobacteria, and Bacteroidetes and a decrease in Firmicutes and Actinobacteria were observed in OSCC patients. The increased bacterial genera were periodontopathogens. The most common viruses were EBV and HPV, especially the high-risk genotypes. Candida was the most studied oral fungus and was always increased in OSCC subjects. Further studies should investigate the possible carcinogenic mechanisms of oral microorganisms found increased in tissue samples and saliva from adult subjects with OSCC.