Carbapenem-resistant Enterobacterales, including KPC-producing Klebsiella pneumoniae, represent a major threat to public health due to their rapid spread. The beta-lactam/beta-lactamase inhibitor (BL/BLI) combination ceftazidime-avibactam (CAZ-AVI) has recently been introduced and shown to exhibit excellent activity toward multidrug-resistant KPC-producing Enterobacterales strains. However, CAZ-AVI-resistant K. pneumoniae isolates are being increasingly reported, mostly corresponding to producers of KPC variants that confer resistance to CAZ-AVI but at a cost of carbapenem resistance. We have characterized here, both phenotypically and genotypically, a clinical CAZ-AVI- and carbapenem-resistant KPC-2 K. pneumoniae isolate co-producing the inhibitor-resistant extended-spectrum beta-lactamase VEB-25.