TMB serves as a predictive biomarker for response to ICIs in head and neck squamous cell carcinoma (HNSCC). Higher TMB in HNSCC is associated with better responses to therapies like pembrolizumab (Keytruda) and nivolumab (Opdivo), as well as Durvalumab and/or Tremelimumab. Pembrolizumab is approved for the treatment of recurrent or metastatic HNSCC with PD-L1 expression (CPS ≥1). Research indicates that high TMB may also be predictive of response to ICIs in these settings. • TMB | NSCLC High TMB has been shown to predict better responses to ICIs in NSCLC. The US FDA has approved pembrolizumab (Keytruda) for use in patients with high TMB (≥10 mutations per megabase) in various cancers, including NSCLC, regardless of PD-L1 expression. Pembrolizumab has been approved for the treatment of NSCLC with high TMB, particularly in patients who have progressed on other therapies. It has shown efficacy in this patient population due to its ability to enhance the immune response against tumors with high TMB. Nivolumab (Opdivo) and ipilimumab (Yervoy): this combination has been studied in patients with high TMB, showing improved outcomes in first-line treatment for NSCLC. The combination leverages the benefits of PD-1 and CTLA-4 inhibition to boost antitumor immunity. Overall, the concept pairs consisting of TMB with colon cancer, HNSCC and NSCLC have fewer publications associated with them (<30) but exhibit a high average fold increase indicating growing interest (Figure and Supporting Information S1).