Our highly specific intratumoral T‐SOX2‐cLNPs offer advantages in both effectiveness and safety, however, this approach is particularly suitable for targeting easily accessible tumors such as those in HNSCC, breast, thyroid, and skin cancer, or cancers with a cancer‐specific target gene, exclusively expressed in cancer cells, crucial for their survival, and associated with poor prognosis and adverse clinicopathological characteristics, like SOX2. This evidence concerns the gene SOX2 and head and neck squamous cell carcinoma.