Background: Complicated pyelonephritis, a severe form of urinary tract infection, poses a significant healthcare burden due to its complex management and potential for severe outcomes. Current understanding of its epidemiological and clinical characteristics remains insufficiently detailed. Aim & Objective: This study aims to analyze the epidemiological, clinical, and microbiological characteristics of patients with complicated pyelonephritis, focusing on identifying key factors influencing prognosis in a tertiary care context. Methods: Conducted at a tertiary care center, this descriptive cross-sectional study enrolled 438 inpatients diagnosed with complicated pyelonephritis. Data on demographic characteristics, clinical presentation, microbiological findings, and patient outcomes were collected and analyzed to discern patterns and correlations. Results: Among the participants, the distribution was 54.6% male and 45.4% female, with a median age of 48 years. The crude mortality rate observed was 6.89%, with an attributable mortality rate of 4.34%. Escherichia coli was the most common pathogen, identified in 68.65% of cases. Significant bacteremia was present in 34.31% of patients, and antimicrobial resistance was notably prevalent. Diagnostic imaging revealed urological anomalies in 60.86% of patients, underscoring the importance of comprehensive diagnostic evaluations. Conclusion: The findings highlight the critical nature of complicated pyelonephritis and the need for precise diagnostic and management strategies, particularly considering the high prevalence of antimicrobial resistance and the impact of urological anomalies on patient outcomes.