Resistance to carbapenems inEnterobacteraleshas become a matter of the highest concern in the last decade. Recently,Enterobacteralesharboring multiple carbapenemases were detected in three hospital centers in Croatia and in the outpatient setting, posing a serious therapeutic challenge for clinicians. In this study, we analyzed eightKlebsiella pneumoniaeand twoEnterobacter cloacaecomplex isolates with multiple carbapenemases, with regard to antibiotic susceptibility, β-lactamase production and plasmid content. The isolates demonstrated uniform resistance to amoxicillin/clavulanate, piperacillin/tazobactam, cefuroxime, ceftazidime, cefotaxime, ceftriaxone and ertapenem. Among novel β-lactam/inhibitor combinations, ceftazidime/avibactam exhibited moderate activity, with 50% of isolates susceptible. All isolates demonstrated resistance to imipenem/cilastatin/relebactam, and all but one to ceftolozane/tazobactam. Four isolates exhibited a multidrug-resistant phenotype (MDR), whereas six were allocated to an extensively drug-resistant phenotype (XDR). OKNV detected three combinations of carbapenemases: OXA-48+NDM (five isolates), OXA-48+VIM (three isolates) and OXA-48+KPC (two isolates). Inter-array testing identified a wide variety of resistance genes for β-lactam antibiotics:blaCTX-M-15,blaTEM,blaSHV,blaOXA-1,blaOXA-2,blaOXA-9, aminoglycosides:aac6,aad,rmt,armandaph, fluoroquinolones:qnrA,qnrB andqnrS, sulphonamides:sul1 andsul2 and trimethoprim:dfrA5, dfrA7, dfrA14, dfrA17 and dfrA19.mcrgenes were reported for the first time in Croatia. This study demonstrated the ability ofK. pneumoniaeandE. cloacaeto acquire various resistance determinants under the selection pressure of antibiotics widely used during the COVID-19 pandemic. The novel inter-array method showed good correlation with OKNV and PCR, although some discrepancies were found.