The dissemination of antimicrobial-resistant bacteria in environmental waters is an emerging concern in medical and industrial settings. In the present study, our research team analyzed superficial water samples from 3 different collection sites along the Ozama River, the most important river in the Dominican metropolitan area. Seventy-six isolates were obtained from culture media previously enriched with cefotaxime and imipenem and subsequently identified by MALDI-ToF. Our isolates spanned 12 genera of bacteria; over 30% were clinically relevant, and 43% exhibited a phenotype classified as multi-drug resistance. The most frequent species identified as Stenotrophomonas maltophilia (n = 33), an emerging nosocomial pathogen. This study constitutes part of the initiative to understand the profiles of the perils of multi-drug resistance in metropolitan areas of the Dominican Republic: a nation with poor antibiotic use regulation.