Background: Managing Pseudomonas aeruginosa bloodstream infections (BSIs) is challenging due to increasing antimicrobial resistance, limited therapeutic options, and high mortality rates. In this study, we aimed to identify 30-day mortality risk factors and assess infectious diseases consultants’ preferences for combination or monotherapy. Methods: The study was conducted in four hospitals in Istanbul, Turkey, involving 140 adult ICU beds and 336,780 ICU-bed-days between 1 January 2014, and 31 December 2021. A total of 157 patients were included in the study. Cox proportional hazard regression was performed to assess the factors on 30-day mortality. Results: The 30-day mortality rate was 44.6% (70/157). Higher Charlson Comorbidity Index (CCI) score, severe sepsis, primary bloodstream infection, being in COVID-19 pandemic period, and infection caused by MDR strain were associated with higher hazard of 30-day mortality. Combination therapy was more commonly used in patients with BSIs with MDR or DTR (difficult-to-treat) strains but did not significantly improve the hazard of 30-day mortality. Conclusions: Targeted interventions and vigilant management strategies are crucial for patients with defined risk factors. While infectious disease consultants tended to favor combination therapy, particularly for drug-resistant strains, our analysis revealed no significant impact on 30-day mortality hazard. The increased incidence of P. aeruginosa BSIs during the pandemic emphasizes the need for infection control measures and appropriate antibiotic prescribing practices.