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Through integrated epigenomic and transcriptomic profiling, we identified a resistance\u2010specific, non\u2010canonical transcriptional circuit driven by the coordinated action of three core components: ID3, SMAD3, and NR2F2. These transcription factors form protein complexes that co\u2010bind to shared enhancers or promoters, reciprocally enhancing each other's transcriptional activity and that of their downstream targets. Mechanistically, ID3 mediates the chromatin residence of the SMAD3\u2010NR2F2 complex through its non\u2010canonical function as a structural co\u2010factor. This rewires the transcriptional program of resistant cells to ultimately drive resistance via direct upregulation of HIF2A, a dual\u2010function hub that concurrently promotes neuroendocrine differentiation and suppresses ferroptosis. Functional studies confirmed that disrupting this circuit or inhibiting its downstream effector HIF2A restored Osimertinib sensitivity in resistant models. 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