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Background MET amplification occurs in approximately 1-5% of treatment-naïve non-small cell lung cancer (NSCLC) cases. It can also develop as an acquired resistance mechanism, particularly after treatment with EGFR tyrosine kinase inhibitors (TKIs), where it’s observed in about 15% of cases.This case underscores the coexistence of MET gene amplification and high PD-L1 expression in NSCLC, which has significant therapeutic implications. The presence of MET amplification suggests potential benefit from MET-targeted therapies, while high PD-L1 expression indicates possible responsiveness to immune checkpoint inhibitors. When MET amplification and high PD-L1 co-exist, the optimal treatment strategy can be challenging. The integration of molecular and immunohistochemical data guides personalized treatment strategies for this patient.Methods A 65 year-old Ex smoker male with advanced non-small cell lung cancer was found to have both high-level MET amplification and high PD-L1 expression (TPS ≥ 50%). Immunohistochemistry confirmed primary lung adenocarcinoma (Jan 2022) and 6 cycle of Palliative first line Chemotherapy with inj. Nab- Paclitaxel + Carboplatin + Denosumab, completed on 11 June 2022 .Results Due to poor response with 1st line CnT, 6 cycle of 2nd line palliative ChT-IO with Atezolezumab + Pemetexed + Carboplatin + Denosumab followed by Maintenance Chemo IO with Pemetrexed + Atezolizumab from 20.03.2023 till on 5/06/23. The follow up 3rd PET scan on Feb 2023 showed that no abdominal lymph nodes and previous osseous lesions are seen but newly appeared Brain lesions revealed on MRI. Maintenance chemotherapy continued along with radiotherapy to brain, and scapula followed by comprehensive genomic profiling (CGP). CGP confirmed the MET amplification. On Follow up 4th PET CT scan on Nov 2023 showed new lesions of Hypermetabolic centimetric low avid multiple soft tissue nodules in right lobe of liver and Hypermetabolic in right para- spinous muscle. Due to poor PS & PD Targeted therapy with Capmatinib (400mg twice daily) started since Nov 2023 and patient hoarseness of voice completely improved also MRI of brain showed no metastatic deposit in brain. Campatinib continue for 6 months and patients progressed with jaundice and poor GC with b/l pedal oedema. Then patient expired after intolerance and jaundice with sepsis on June 2024.Conclusions This case highlights the complexities of managing NSCLC with co-occurring MET amplification and high PD-L1, underscoring the importance of comprehensive molecular profiling and personalized treatment strategies. Further research into the coexistence of these biomarkers may enhance understanding of tumor behavior and resistance mechanisms.