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Introduction: Mesenchymal-epidermal transition factor gene amplification ( MET amp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary MET amp, as well as the testing procedures used to identify MET amp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for MET amp were also examined., Methods: Embase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015-2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020-2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps., Results: The median rate of primary MET amp in NSCLC across the references was 4.8% (n=4 studies) and of secondary MET amp (epidermal growth factor receptor [ EGFR ]-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence in situ hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). MET amp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: MET copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of MET amp NSCLC. Promising preliminary results from trials enrolling patients with EGFR -mutated, MET amp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level MET amp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines., Conclusion: Primary MET amp occurs in approximately 5% of NSCLC cases, and secondary MET amp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating MET amp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed., Competing Interests: Authors MY, FL, and RH were employed by the company EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA, at the time of the study. Authors EM and BL were employed by the company OPEN Health at the time of this study, which was the recipient of consulting fees from EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA. Author RS received honoraria from AstraZeneca, and Amgen; attended advisory boards and provided consulting for AstraZeneca, EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA, Daiichi Sankyo, Lilly, Janssen Oncology, Macrogenics, Sanofi/Aventis, Regeneron, Mirati Therapeutics, and GlaxoSmithKline; received research funding from Merck, AstraZeneca Investigator-sponsored trials, and BMS Institution research funding., (Copyright © 2024 Yang, Mandal, Liu, O’Hara, Lesher and Sanborn.)