Proteus mirabilis is one among the most frequently identified pathogen in patients with the urinary tract infection. The multidrug resistance exhibited by P. mirabilis renders the treatment ineffective, and new progressive strategies are needed to overcome the antibiotic resistance (AR). We have analyzed the evolutionary relationship of 29 P. mirabilis strains available in the National Center for Biotechnology Information-Genome database. The antimicrobial resistance genes of P. mirabilis along with the enriched pathways and the Gene Ontology terms are analyzed using gene networks to understand the molecular basis of AR. The genes rpoB, tufB, rpsl, fusA, and rpoA could be exploited as potential drug targets as they are involved in regulating the vital functions within the bacterium. The drug targets reported in the present study will aid researchers in developing new strategies to combat multidrug-resistant P. mirabilis. © 2020 Wiley Periodicals LLC