The combination of amivantamab and lazertinib demonstrates therapeutic potential in patients with EGFR-mutated advanced non-small cell lung cancer, targeting both the receptor and downstream signaling pathways simultaneously. This dual-agent approach addresses a critical challenge in oncology where single-target therapies often face resistance mechanisms. EGFR mutations drive approximately 10-15% of lung cancers in Western populations and up to 50% in Asian populations, making this a significant patient subset. The bispecific antibody amivantamab blocks EGFR while also targeting MET receptor, potentially preventing common escape mechanisms. Meanwhile, lazertinib serves as a third-generation tyrosine kinase inhibitor designed to overcome resistance mutations like T790M. This combination strategy represents the evolving paradigm toward multi-target cancer therapy, moving beyond the limitations of sequential single-agent treatments. However, dual-agent regimens typically introduce greater toxicity concerns and cost considerations. The clinical significance will ultimately depend on progression-free survival improvements, overall survival benefits, and tolerability compared to current standard-of-care options like osimertinib monotherapy. This approach could particularly benefit patients with complex resistance patterns or those seeking to delay treatment progression.