Carbapenem-resistant Enterobacterales (CRE) infections, which are associated with high morbidity and mortality, are increasingly reported worldwide, particularly in healthcare settings. This observational study investigated patients with CRE infections at an Indian tertiary care hospital. The infections predominantly affected elderly individuals: the 61–80 age group accounted for 59.4% of cases, while the 71–80 subgroup alone comprised 38.6% of patients. Regarding hospital stay duration, nearly half of the patients (48.3%) were hospitalized for 0–10 days, whereas 31.0% remained hospitalized for 31 days or more. The most frequently utilized indwelling devices were Foley catheters, followed by nebulizers, nasogastric (NG) tubes, and ventilators. Microbiologically, Klebsiella pneumoniae was the primary isolate (58.6%), followed by Escherichia coli (27.3%), Pseudomonas aeruginosa (6.1%), Acinetobacter baumannii (2.0%), non-lactose fermenters (2.0%), and Providencia rettgeri, Enterobacter cloacae, and Aspergillus spp. (2.0% each). This study highlights the clinical and microbiological characteristics of CRE isolated from hospitalized patients. Genetic analysis revealed that blaNDM and blaOXA-48 were the most prevalent carbapenemase genes, while blaKPC and blaIMP occurred less frequently. Notably, several isolates co-harbored multiple resistance genes (such as blaNDM and blaOXA-48, suggesting the emergence of multidrug-resistant variants with complex resistance determinants.