The World Health Organization (WHO) has recognized antimicrobial resistance to be one of the top 10 threats to mankind in the coming future. Therefore, it requires solutions that are targeted, sustainable, and economically effective. Carbapenem-resistant Pseudomonas aeruginosa is associated with nosocomial infections affecting mostly patients with chronic lung disease. The goal of the current investigation was to gain insight into significant P. aeruginosa genes responsible for carbapenems, beta-lactams, and other antimicrobials resistance through a systems biology approach. To proceed with the methodology, 866 genes were retrieved from the NDARO database and a gene interaction network of 45 genes and 195 functional partners was constructed using STRING v9.0 with high confidence and analyzed using Cytoscape 3.10.0. Using clustering analysis, four closely linked clusters (C1-C4) associated with mechanisms of multidrug-resistance were identified. The enrichment analysis revealed a substantial role for 43 genes in biological processes, 36 genes in molecular function, and 40 genes in cellular components. The gene interaction network analysis found that the genes oprD, oprM, oprN, mexR, nfxB, mexB, mexT, mexA, nalD, and nalC had the greatest number of gene interactions, which can be further used as potential drug targets for the development of novel therapeutics to manage the antimicrobial resistance associated with Pseudomonas aeruginosa.