Pseudomonas aeruginosa is a leading cause of healthcare-associated infections, which are related to substantial morbidity and mortality. The incidence of Plasmid-Mediated Quinolone Resistance (PMQR) determinants has been previously reported in this bacterium. However, there is limited information regarding the presence of PMQR and carbapenemase-encoding genes simultaneously. This study aims to analyze the prevalence of these determinants on P. aeruginosa strain isolated from clinical patients in the State of Aguascalientes, Mexico. Fifty-two P. aeruginosa isolates from nosocomial patients were collected from Centenario Hospital Miguel Hidalgo. This is a retrospective observational study conducted at a single center. Antibiotic susceptibility was tested using the Vitek-2 system. Only carbapenem-resistant isolates were included in this study. Carbapenemase-encoding genes and PMQR determinants were screened by polymerase chain reaction (PCR). Resistance rates of 100% were found on tigecycline and ceftriaxone. Of the 52 isolates, 34.6% were positive for the qnr genes, 46.2% for the oqxA gene, and 25% for the aac-(6′)-lb gene. The most frequent carbapenemase genes found in the samples were bla_OXA-51 (42.3%), bla_OXA-1 (15.4%), and bla_VIM (15.4%). bla_OXA-51 co-carrying oqxA was detected in 21.1% of the isolates, bla_OXA-51 co-carrying aac-(6’)-lb in 11.5%, bla_VIM co-carrying aac-(6′)-lb in 3.8%, and bla_KPC co-carrying oqxA in 5.8%. Systematic surveillance to detect carbapenemase-encoding genes and PMQR determinants, and rational prescription using the last-line drugs could help in preventing the dissemination of multidrug-resistant determinants.