Nosocomial infections (NIs) are a significant global health issue, specifically in intensive care units (ICUs). The study aims to identify the bacterial profiles and antimicrobial resistance patterns of NI pathogens in the ICU of a tertiary care hospital, with the goal of informing effective treatment and infection control approaches. This cross-sectional, descriptive study was conducted between March 2024 and March 2025 in the ICUs of Saidu Teaching Hospital. Clinical samples were collected from patients who had acquired signs of infection after 48 h of admission. Identification and antimicrobial susceptibility of bacteria were conducted using standard microbiological and Kirby–Bauer disc diffusion techniques. Multidrug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. Among 450 admitted patients, 112 (24.9%) had clinical NIs, and 98 (21.8%) were microbiologically verified. Gram-negative bacilli predominated (78.6%), followed by Acinetobacter baumannii (27.7%) and Pseudomonas aeruginosa (21.4%). Ventilator-associated pneumonia (45.5%) and catheter-associated urinary tract infections (28.6%) were the most common sites of infection. The prevalence of MDR was alarming, 76.8% overall, with 100% of A. baumannii and K. pneumoniae being MDR. Carbapenem resistance was found to be high (A. baumannii: 93.5, K. pneumoniae: 72.2). Most Gram-negative isolates were mostly susceptible to colistin. NIs tend to have a high burden in the ICU, as observed in this study, particularly with Gram-negative bacteria that exhibit MDR. The extreme prevalence of carbapenem-resistant A. baumannii and K. pneumoniae signals an highlights a crisis in antimicrobial resistance. These findings underscore the importance of implementing robust infection prevention and control policies, executing rigorous antibiotic stewardship initiatives, and maintaining ongoing local surveillance to inform empirical treatment and improve patient outcomes.