Background: Metallo-β-lactamase (MBL)-producing Gram-negative bacteria, particularly those co-expressing serine β-lactamases, pose a major global health threat due to limited treatment options. In Egypt, blaNDM-1 and blaOXA-48 are prevalent in clinical settings. While ceftazidime-avibactam (CZA) is the only available β-lactam/β-lactamase inhibitor (BL/BLI) combination, its limited efficacy against locally prevalent carbapenem-resistant isolates necessitates alternative strategies. Aim: To evaluate the activity of the CZA-aztreonam (ATM) combination against carbapenem-resistant Gram-negative (CR-GN) isolates, particularly MBL producers, either alone or co-producing serine carbapenemases. Methods: Thirty-four non-duplicate CR-GN isolates were collected from hospitalized patients in Egypt. Carbapenemase genes were identified via multiplex PCR, and Susceptibility to CZA and ATM combination was assessed using the CLSI-endorsed broth disc elution method. Fisher's exact test was used for statistical comparisons. Results: Klebsiella pneumoniae (52.9%) was the most common isolate, followed by Acinetobacter spp. (29.4%), Pseudomonas aeruginosa (P. aeruginosa) (11.8%), E. coli and Proteus spp. (2.9% each). The bla_NDM gene was detected in 91.2% of isolates, bla_OXA-48 in 64.7%, with 52.9% co-harboring both. Overall, 76.5% of isolates were susceptible to the CZA-ATM combination, including 69.2% of CZA-resistant isolates. Among CZA-resistant isolates, susceptibility to CZA+ATM was higher among Enterobacterales (82.4%), compared to Acinetobacter spp. (50%) and P. aeruginosa (0%). Conclusions: The ATM-CZA combination demonstrates promising in vitro efficacy against MBL-producing Enterobacterales but shows limited activity against P. aeruginosa and Acinetobacter spp. Key limitations include the small sample size and the study's in vitro design. Further clinical studies and resistance monitoring are necessary to guide treatment decisions and optimize therapeutic strategies.