Objective: To conduct a prospective study of the prevalence of pathogens and their susceptibility to drugs in chronic suppurative otitis media (CSOM) in the Taklamakan Desert region of Xinjiang, and to provide a basis for the treatment of chronic suppurative otitis media in this area. Method: CSOM patients treated at the Third Division General Hospital of Xinjiang Production and Construction Corps from January 30, 2024 to November 30, 2024 were selected as the study subjects. Pus from the affected ear was cultured for pathogen isolation and drug susceptibility testing, and the distribution of pathogens and drug sensitivity was statistically analyzed. Results: A total of 176 patients were included in this study, with 121 cases (68.8%) yielding pathogens. A total of 122 strains of pathogens were identified, with 73 Gram-positive bacteria (59.8%), predominantly Staphylococcus aureus (SA) (66 strains, 54.1%), including 54 methicillin-sensitive SA (MSSA) strains (44.3%) and 12 methicillin-resistant SA (MRSA) strains (9.8%); 32 Gram-negative bacteria (26.2%), predominantly Pseudomonas aeruginosa (PA)(17 strains, 13.9%); and 17 fungi (13.9%), predominantly filamentous fungi (13 strains, 10.7%). Drug susceptibility testing showed that MSSA had high resistance rates to penicillin, erythromycin, and clindamycin, but was sensitive to oxacillin, levofloxacin, linezolid, rifampin, tigecycline, and vancomycin; MRSA showed high resistance to oxacillin, erythromycin, clindamycin, quinolones, and other commonly used drugs, but was sensitive to gentamicin, co-trimoxazole, linezolid, rifampin, tigecycline, and vancomycin. Gram-negative bacteria had a high resistance rate to cefuroxime, but were sensitive to ceftazidime, cefepime, gentamicin, imipenem, meropenem, and other drugs. Conclusions: The main pathogens causing CSOM in the Taklamakan Desert region of Xinjiang are SA, PA, and filamentous fungi, with relatively high infection rates of MRSA and fungi. Early completion of bacteriological and mycological analysis can lead to more targeted treatment, shorten the course of the disease, and improve therapeutic outcomes.