Background: Antimicrobial resistance (AMR) in intensive care units (ICUs) is driven by high antibiotic exposure, invasive procedures, severe illness, and frequent circulation of multidrug-resistant organisms. ICU-specific antibiograms can support empirical therapy, optimize stewardship, and improve outcomes. Objective: To characterize microbial epidemiology, define antimicrobial resistance burden, construct an ICU antibiogram, and identify sensitive agents that may support empirical therapy. Methods: A prospective observational microbiology-based study was conducted among 100 critically ill patients admitted to a tertiary care ICU. Culture and sensitivity reports were analysed to determine organism distribution, gram-stain epidemiology, resistance burden, susceptibility patterns, and disease-specific antibiograms. Descriptive analysis, resistance comparisons, and exploratory associations were performed. Results: Gram-negative organisms predominated (79.1%), while gram-positive organisms accounted for 20.9%. E. coli (38.18%) was the most common isolate, followed by Klebsiella species (23.63%) and Pseudomonas species. Meropenem, amikacin, gentamicin, and piperacillin–tazobactam showed higher sensitivity profiles, whereas ampicillin, cefepime, ceftriaxone, and cotrimoxazole demonstrated substantial resistance. Resistance burden was highest for cephalosporins (31%) and penicillins (29%). Disease-specific antibiograms suggested E. coli predominance in urinary tract infections, Pseudomonas in sepsis, and Klebsiella in pneumonia. Conclusion: ICU-specific resistance burden is driven predominantly by gram-negative pathogens, supporting the importance of local antibiogram-guided empirical therapy, stewardship interventions, and resistance surveillance.