Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, with increasing antimicrobial resistance compromising empirical therapy. This multicenter cross-sectional study evaluated the bacterial spectrum and antimicrobial susceptibility patterns of uropathogens isolated from catheter-associated and non-catheter-associated UTIs in three tertiary care hospitals in Peshawar, Pakistan, between January 2022 and June 2023. Of 1,886 urine specimens, 1,694 (89.8%) yielded significant bacterial growth. Escherichia coli (43.0%) was the predominant pathogen, followed by Citrobacter spp. (15.6%), Morganella morganii (15.1%), Pseudomonas spp. (9.7%), and Klebsiella pneumoniae (9.3%). Carbapenems, amikacin, tigecycline, nitrofurantoin, fosfomycin, and cefoperazone–sulbactam demonstrated the highest in vitro activity, whereas fluoroquinolones, third-generation cephalosporins, aminopenicillins, and co-trimoxazole showed high resistance rates. These findings underscore the need for continuous antimicrobial resistance surveillance, routine institutional antibiograms, evidence-based revision of empirical treatment guidelines, and strengthened antimicrobial stewardship programs to optimize UTI management.