Background. Ceftazidime-avibactam (CZA) and meropenem-vaborbactam (MVB) are novel therapeutic options for infections caused by carbapenem-resistant Enterobacterales (CRE). Our study aimed to evaluate the in vitro activity of CZA and MVB, against a diverse collection of CRE and to assess the accuracy of the disc diffusion method compared to E-test. Methods. 70 CRE isolated from hospitalized patients in Egypt were included in our study. The in vitro susceptibility profiles of these isolates to CZA and MVB were determined using disc diffusion and E-test methodologies. The studied isolates were genetically identified as part of another study using multiplex-PCR. Results. Susceptibility rates to CZA and MVB were low, at 31.4% and 14.3%, respectively with the best activity of CZA reported among isolates harboring OXA-48 gene alone followed by isolates producing a combination of OXA-48 and NDM-1 (50%, 42.9%, respectively) while the least activity recorded was against NDM-1 only producers (11.5%). The highest susceptibility rate for MVB was recorded among isolates harboring NDM-1 gene alone followed by the dual carbapenemase producers (19.2%, 11.9%, respectively) while the least activity was among OXA-48 only producers. The categorical agreement (CA) between disc diffusion and E-test of CZA and MVB was acceptable with low very major error (VME). However, a high major error (ME) was recorded. Conclusions. CZA and MVB have shown limited effectiveness against studied CRE isolates. Disc diffusion tests for CZA and MVB may not be reliable substitutes for E-tests. A comprehensive understanding of test performance within specific clinical settings is essential prior to definitive interpretation.