In vivo studies were conducted in NSCLC (NCI-H358) cell-derived tumor xenograft model.<h4>Results</h4>Our research has shown promising activity of omeprazole, a V-ATPase-driven proton pump inhibitor with potential anti-cancer properties, in combination with the MET inhibitor tepotinib in KRAS-mutant G12C and non-G12C NSCLC cell lines, as well as in G12C inhibitor (AMG510, sotorasib) and MEK inhibitor (trametinib)-resistant cell lines. Here, MET is linked to cancer.