ABSTRACT Immunotherapy has transformed the treatment of non‐small cell lung cancer (NSCLC), yet most patients fail to respond due to poorly understood resistance mechanisms. Here, integrative multi‐omics analysis combining single‐cell RNA‐sequencing, bulk RNA‐seq, and spatial transcriptomics is performed on tumors from NSCLC patients receiving immune checkpoint blockade (ICB). Transcriptomic profiling revealed that GALNT7, a glycosyltransferase, is selectively upregulated in non‐responders (NR)