Background: Chronic Suppurative Otitis Media (CSOM) is a persistent middle ear infection with significant morbidity, particularly in developing countries. The evolving microbial profile and increasing antibiotic resistance necessitate periodic evaluation of prevalent pathogens and their susceptibility patterns to optimize treatment strategies. Objective: To assess recent trends in the microbiology of CSOM and evaluate the antibiotic susceptibility patterns of the isolated pathogens in a tertiary care hospital in India. Methods: This prospective, cross-sectional study was conducted in a tertiary care hospital. Middle ear discharge samples from patients diagnosed with CSOM were collected and processed for microbial culture. Bacterial isolates were identified, and antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Klebsiella species (35.6%), Pseudomonas aeruginosa (28.4%), and Staphylococcus aureus (21.1%) were the predominant isolates. High resistance was noted against Cotrimoxazole (52.38%) and Ciprofloxacin (39.05%), while Piperacillin/Tazobactam (80.77%) and Netilmicin (77.14%) exhibited the highest sensitivity. No statistically significant difference was observed in ciprofloxacin resistance (p = 0.395). Conclusion: CSOM continues to evolve with shifting microbial patterns and increasing antimicrobial resistance. Culture-guided therapy is essential for effective management, and routine microbiological surveillance is recommended to update empirical treatment protocols.