Background/Objectives: Chronic otomastoiditis is a complex inflammatory condition frequently associated with delayed diagnosis, inadequate antibiotic use, and healthcare disparities. This study aimed to analyze the clinical, demographic, and microbiological characteristics of chronic otomastoiditis and its complications over a 10-year period in rural versus urban populations. Methods: This retrospective study included 292 patients with chronic otomastoiditis admitted to the ENT Clinic of Craiova County Emergency Clinical Hospital from 2013 to 2023. Data were collected on patient demographics, clinical presentations, imaging findings, audiometry, bacteriological profiles, and surgical outcomes. Statistical analyses were conducted to identify risk factors and patterns of antibiotic resistance. Results: Urban patients represented 60.27% of cases, while rural patients (39.73%) presented later with more advanced disease. Cholesteatoma was identified in 49.31% of cases, frequently associated with hearing loss and structural complications. Significant antibiotic resistance was noted for Streptococcus pneumoniae and Staphylococcus aureus, with high resistance rates to amoxicillin and amoxicillin–clavulanate. Surgical interventions, primarily mastoidectomy, were associated with varied recovery rates and complications. Conclusions: Chronic otomastoiditis is influenced by healthcare accessibility and antibiotic resistance. Early diagnosis, antibiotic stewardship, and targeted surgical interventions are critical in managing this condition, particularly in underserved rural populations. Public health efforts should focus on improving healthcare accessibility to mitigate long-term complications.