The present work identified that CAFs‐derived Exos transferred miR‐3126‐5p to NSCLC cells, which targeted and inhibited KLF13 expression to facilitate SH2B1 transcription, and subsequently interacted with IRS1 to activate the PI3K/AKT pathway, thereby promoting glycolysis to drive NSCLC progression. Here, IRS1 is linked to non-small cell lung carcinoma.