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The rise in multiple-drug-resistant (MDR) phenotypes in Gram-negative pathogens is a major public health crisis. <i>Pseudomonas aeruginosa</i> is one of the leading causes of nosocomial infections in clinics. Treatment options for <i>P. aeruginosa</i> have become increasingly difficult due tdo its remarkable capacity to resist multiple antibiotics. The presence of intrinsic resistance factors and the ability to quickly adapt to antibiotic monotherapy warrant us to look for alternative strategies like combinatorial antibiotic therapy. Here, we report the frequency of <i>P. aeruginosa</i> multidrug-resistant and extensively drug-resistance (XDR) phenotypes in a super-specialty tertiary care hospital in north India. Approximately 60 percent of all isolated <i>P. aeruginosa</i> strains displayed the MDR phenotype. We found highest antibiotic resistance frequency in the emergency department (EMR), as 20 percent of isolates were resistant to 15 antipseudomonal antibiotics. Presence of plasmids with quinolone-resistance determinants were major drivers for resistance against fluoroquinolone. Additionally, we explored the possible combinatorial therapeutic options with four antipseudomonal antibiotics—colistin, ciprofloxacin, tobramycin, and meropenem. We uncovered an association between different antibiotic interactions. Our data show that the combination of colistin and ciprofloxacin could be an effective combinatorial regimen to treat infections caused by MDR and XDR <i>P. aeruginosa</i>.