Objective: In this overview, we present compelling evidence from multiple systematic reviews and meta-analyses (SRMAs) and examine the prognostic role of the PD-L1/PD-1 axis, as well as the potential of personalized treatment strategies targeting this axis, in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). The gene discussed is CD274; the disease is oral cavity squamous cell carcinoma.