Introduction: Pseudomonas aeruginosa is a bothersome pathogen on the rise and prone to developing resistance during treatment. Hospitalized patients are especially prone to its detrimental effects. Aims: To determine the prevalence and antimicrobial susceptibility pattern of Mono therapy and combination therapy of Cefepime in Pseudomonas aeruginosa isolates obtained from patients at a tertiary care hospital in Karachi, Pakistan. Methods: This study was conducted at a university-affiliated, urban teaching hospital. During a 2-year period (January 2013 to December 2015), all hospitalized patients with a positive blood culture for P. aeruginosa were eligible for this investigation, amounting to a sample size of 634, and a cross sectional study was performed. Standard microbiological methods were used to identify the clinical isolates. The isolates were cultured on chocolate and MacConkey agar. Results: Throughout the duration of this study, 634 isolates of P. aeruginosa were cultured. Positive cultures were then tested against the following drugs: Cefepime, Meropenem, Amikacin and Ciprofloxacin. Cefepime was 76.2% (483) sensitive for isolates while the age and sex relationship analysis showed that isolates gathered from 0-18 year old females were 94.6% sensitive to Cefepime. Around 63.25% isolates were sensitive to the combination of Cefepime and Amikacin while the combination offering the least resistance was that of Cefepime and Ciprofloxacin (7.1%). Conclusions: P. aeruginosa isolates show a progressive trend of resistance to Cefepime. Cefepime when used in combination with Ciprofloxacin, potentially will be more effective than monotherapy with Cefepime.