Pseudomonas aeruginosa is a common gram-negative bacillus in nosocomial settings. Consideration of this organism is important due to its potential to acquire multi-drug resistance through various mechanisms causing severe infections, particularly in immunocompromised hosts. Here, we present a challenging case of a blood stream infection caused by a drug-resistant strain of P. aeruginosa in a debilitated young patient. A 31-year-old male patient with a complex history of multiple trauma following a vehicle accident that required several surgical interventions, is plagued by persistent bacteremia. An extensively drug-resistant strain of P. aeruginosa was repeatedly isolated that continued to grow in the patient's blood cultures despite treatment with meropenem and colistin for an extended period. In addition to phenotypic characterization, the complete genome of the strain was sequenced and a genomic view was provided regarding its antimicrobial resistance (AMR) patterns, efflux pump genes, virulence determinants, phageomic signals, and genomic islands. The strain belongs to sequence type ST357 with dominant Class A (VEB), Class B, Class C (PDC-11) and D (OXA-10, OXA-50) β-lactamases, and injectosomes (type III secretion system) known to mediate high virulence. The pool of extended spectrum β-lactamases genes and the upregulated chromosomal efflux system are likely to account for the extended resistance pattern in this strain. In light of the global spread of ST357 isolates, it is essential to continue monitoring their resistance patterns and evaluate effective epidemiological tools to define the genetic determinants of emerging resistance. Intensified infection control measures are continuously required to stop dissemination of such strains in an institution where susceptible hosts are at risk of acquiring them.