Background: Urinary tract infections (UTIs) are a major source of antibiotic use, with increasing antimicrobial resistance compromising treatment efficacy. This study evaluates local pathogen distribution and resistance patterns to support empirical therapy. Methods: We conducted a retrospective, observational study analyzing all positive urine cultures obtained in a tertiary care hospital between January 2023 and December 2025. Bacterial identification and antimicrobial susceptibility testing were performed using routine microbiological methods. Susceptibility results were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Results: A total of 1,298 bacterial isolates recovered from positive urine cultures obtained between January 2023 and December 2025 were included in the analysis. Antimicrobial resistance was assessed using 18,079 individual antimicrobial susceptibility test (AST) results. Gram-negative bacteria predominated, with Escherichia coli (44.5%) and Klebsiella pneumoniae (20%) accounting for approximately 64.5% of all isolates. E. coli exhibited high resistance rates to ampicillin (60.4%) and trimethoprim–sulfamethoxazole (33.8%), while resistance to fluoroquinolones was considerable (25.9%). In contrast, nitrofurantoin (2.0%) retained excellent activity, and carbapenem resistance remained very low (0.4%). Klebsiella pneumoniae demonstrated extremely high resistance to beta-lactams and fluoroquinolones, with resistance to third-generation cephalosporins exceeding 60% and carbapenem resistance reaching 34.5–41.2%. Among Gram-positive pathogens, Enterococcus faecalis showed high resistance to fluoroquinolones and high-level aminoglycosides, whereas susceptibility to nitrofurantoin, linezolid, tigecycline, and glycopeptides remained largely preserved. The prevalence of vancomycin-resistant Enterococcus (VRE) was low (7.9%). Conclusions: Our findings reveal alarmingly high resistance rates among major pathogens, particularly Klebsiella pneumoniae, significantly limiting empirical therapeutic options. Nitrofurantoin remained highly active in our cohort. In accordance with current international guidelines, nitrofurantoin and fosfomycin remain recommended first-line agents for uncomplicated UTIs. Continuous local surveillance is essential to guide empirical therapy and support antibiotic stewardship efforts.