Carbapenem-resistance in Gram-negative bacteria poses a global threat, necessitating vigilant surveillance for informed policy decisions. Our study investigated clinically significant, carbapenem-resistant Enterobacterales infections. The analysis involved documenting data on clinical specimens received, antibiogram, treatment given and relevant clinical details sourced from medical records. Statistical analyses aimed to understand the association between risk factors and mortality outcomes. Out of 280 cases, most were males (71.1%), aged over 65 (49.6%), with a mortality rate of 14.6%, significantly linked to age (p < 0.001*). Skin/soft tissue (36.7%) and respiratory (34.29%) infections exhibited the highest CRE isolation rates, mainly attributed to Klebsiella pneumoniae (69.2%). Infection type significantly influenced mortality (p < 0.05). Factors like prior hospitalization/surgery, antibiotic exposure, chemotherapy, COVID status, ICU duration, mechanical ventilation, and indwelling devices were associated with mortality (p < 0.05) on univariate analysis. Multivariate analysis for infection type, clinical sample, organism, and prior carbapenem use was significant (p < 0.05). Cotrimoxazole, aminoglycosides and tigecycline displayed sensitivity in a substantial portion of CRE cases. Betalactams/Betalactam inhibitor monotherapy was the most commonly administered empiric antibiotic (survival rate-76.19%). Majority (76.4%) received combination therapy (Beta-lactam inhibitor with colistin/tigecycline/carbapenem), with 87.85% survival rate. Thus, continuous monitoring and review of the risk factors and antibiogram of CRE cases, would help to adapt to the changing antibiotic resistance patterns. The action plan could prioritize the use of Cotrimoxazole and aminoglycosides for empirical treatment. Specific pathogen driven, targeted combination therapy using aminoglycoside and Polymyxin B-based regimens showed no recorded instances of mortality.