Background: Bloodstream infections (BSIs) caused by Pseudomonas aeruginosa have high mortality rates and pose a significant threat to healthcare settings. Objectives: We aimed to investigate the clinical risk factors related to mortality and the development of P. aeruginosa with difficult-to-treat resistance (DTR-PA) BSI in the intensive care unit. Methods: This was a retrospective, single-center study that included patients with P. aeruginosa BSI who were hospitalized between 2020 and 2022. The risk factors affecting 30-day mortality and the development of DTR-PA were investigated using both univariate and multivariate analyses. Results: A total of 140 patients were analyzed. The mean age was (66 ± 17.5) years, and 48% of the patients were male. Previous meropenem use was an independent risk factor for DTR-PA BSI (odds ratio, 2.68; 95% CI, 1.24 to 5.80; P = 0.012). Multivariate analysis demonstrated that the requirement for inotropic support was an independent risk factor for 30-day mortality [hazard ratio, 2.50; 95% confidence interval (CI), 1.33 to 4.68; P = 0.004]. Conclusions: Prior meropenem use was an independent risk factor for DTR-PA development. Strict policies for Carbapenem use and infection control procedures are essential to combat infections caused by DTR-PA.