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Although EGFR\u2010targeted tyrosine kinase inhibitors (TKIs) initially provide clinical benefits, resistance inevitably develops. Targeted protein degradation (TPD) offers a paradigm shift in cancer therapy by eliminating pathogenic proteins entirely, rather than merely inhibiting their function. This review comprehensively examines TPD strategies for lung cancer treatment, focusing on EGFR as an exemplary target. We trace the evolution of proteolysis targeting chimeras (PROTACs) from first\u2010generation compounds to sophisticated degraders with enhanced selectivity and potency. Structural insights from AlphaFold3 predictions reveal critical EGFR features that guide rational degrader design. We systematically compare EGFR\u2010targeting PROTACs, evaluating their degradation kinetics, mutant selectivity, and clinical potential. Beyond traditional small\u2010molecule PROTACs, we explore emerging modalities\u2014including peptide\u2010based, antibody\u2010based, and nucleic acid\u2010based degraders\u2014each offering unique advantages for overcoming current therapeutic limitations. We also discuss alternative TPD strategies, namely, molecular glues and lysosome\u2010targeting chimeras (LYTACs), which expand the therapeutic arsenal against EGFR. Importantly, we identify resistance mechanisms specific to protein degraders: E3 ligase loss or mutation, EGFR alterations that disrupt ternary complex formation, deubiquitinase upregulation, and degradation pathway dysfunction. 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