Highlights • CRKP-derived outer membrane vesicles (OMVs) serve as multifunctional vectors for antibiotic resistance, encapsulating a diverse array of lipids and harboring the carbapenemase gene bla KPC . • Meropenem stress triggers a marked upregulation of membrane lipids in CRKP-OMVs, particularly sphingolipids (SP), glycerolipids (GL), glycerophospholipids (GP), and fatty acids (FA), which likely fortify bacterial antibiotic resistance through enhanced membrane stability and efflux efficiency. • CRKP-OMVs mediate horizontal gene transfer of bla KPC-2 to both intra- and interspecies susceptible bacteria, with meropenem-induced lipid remodeling significantly boosting transformation efficiency—a potential accelerator for environmental resistance spread.