Notably, we discovered that SPP1+ TAM subpopulation activated energy metabolism and angiogenesis-related pathways, suggesting that SPP1+ TAM subpopulation, by regulating energy metabolism and altering the tumor microenvironment, promote angiogenesis to supply resources for tumor growth and migration, ultimately mediating poor prognosis in HNSCC patients. The gene discussed is SPP1; the disease is head and neck squamous cell carcinoma.