Carbapenem-resistant K. pneumoniae (CRKP), listed in the WHO 2024 priority, hydrolyzes β-lactam antibiotics, especially carbapenems, posing a significant challenge. Carbapenems are the last resort antibiotics for severe Gram-negative infections and are associated with increased mortality in ICUs and IPDs. This cross-sectional study at a tertiary hospital (April 2023-December 2024) included 375 multidrug-resistant (MDR) K. pneumoniae isolates with ertapenem MIC ≥8 µg/mL. Carbapenemase genes were detected via conventional PCR. Bivariate analysis examined clinical correlations, while MIC50/90 assessed resistance. The most common carbapenemase genes were blaNDM (48.26%) and blaOXA-48 (37.86%), followed by blaKPC (13.6%). Co-occurrence of genes was also reported. Twelve of seventeen clinical variables were significantly associated with gene presence (p < 0.05). Ertapenem, imipenem, and meropenem had MIC50/90 ≥8 µg/mL, indicating high resistance. Tigecycline showed better sensitivity, with MIC50/90 of 0.5/2 µg/mL (blaNDM) and 2/2 µg/mL (blaOXA-48). Fosfomycin MIC90 in blaOXA-48 isolates ranged up to 256 µg/mL. The study highlights high blaNDM and blaOXA-48 prevalence, their clinical associations, and limited therapeutic options. Tigecycline remains most effective in vitro, but pharmacokinetic concerns exist. These findings emphasize the need for antimicrobial stewardship and molecular surveillance.