Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterised by impaired mucociliary clearance, chronic inflammation, and persistent bacterial infections of the lungs. Pseudomonas aeruginosa (Pa) is the predominant pathogen associated with progressive lung damage, morbidity, and mortality in CF patients. In chronic infections, temperate bacteriophages can integrate into the Pa genome, introducing genetic elements that influence bacterial adaptation, virulence, and long-term evolution within the CF lung environment. In this project, we adopted a “reverse engineering” approach to directly investigate the contribution of temperate phages to Pa physiology and evolution that could contribute to the pathophysiology of the chronically infected lung. Using CRISPR interference (CRISPRi), we selectively targeted temperate phage regions in clinical isolates from CF patients, as well as in the well-characterized laboratory strains PAO1 and PA14. The resulting phage-cured strains were then examined using untargeted metabolomics and RNA sequencing to assess global changes in gene expression and metabolic activity. These analyses revealed significant shifts in the cellular metabolome and transcriptome, suggesting that temperate phages play an active role in modulating host metabolism and adaptation. This study provides new insight into how integrated phages may shape physiological behavior of P. aeruginosa during chronic infection in the CF lung.