Abstract: The MET gene is an important tumor-driving gene for non-small cell lung cancer (NSCLC). Drugs targeting tumor with MET exon 14 skipping mutations bring new hope for patients. Although MET inhibitors such as tepotinib and savolitinib have shown good antitumor effects, resistance is inevitable. Studies on the hepatocyte growth factor (HGF)/mesenchymal- epithelial transition factor (MET) signaling pathway will not only help explore the mechanism underlying resistance to MET inhibitors, they may aid in the discovery of strategies for inhibiting and reversing drug resistance, thereby expanding the field of novel drug development. Preliminary studies have shown that the combination of HGF/MET inhibitors with other drugs may have great potential for clinical applications. This article reviews the characteristics of MET gene abnormalities, the mechanism of resistance against MET inhibitors, and the strategies for responding to resistance. Finally, the challenges posed by MET inhibitors is discussed and guidance on the direction of future development of MET inhibitors is proposed.