A preclinical study using mEERL95 cells, which are mouse‐derived HPV‐positive HNSCC models, found that chronic metformin treatment significantly reduced tumor growth velocity (> 50%, p < 0.0001) and increased the CD8+/T‐reg ratio, leading to enhanced tumor immune infiltration. These findings suggest that long‐term metformin administration may potentiate immune checkpoint inhibitors by modulating the tumor immune microenvironment. Here, TBXT is linked to head and neck squamous cell carcinoma.