The presence of multidrug-resistant organisms, often known as MDROs, is a significant risk to public health all over the world. Pseudomonas aeruginosa clinical isolates continue to be one of the most researched MDROs; nevertheless, there is a lack of information in Pakistan about the sensitivity of its animal and plant isolates to antipseudomonal drugs. Pseudomonas aeruginosa was isolated from 25 vegetable samples, 25 animal samples, and 50 clinical samples, for a total of 100 samples. Standard biochemical techniques were used to determine the identities of all the isolates. One hundred P. aeruginosa isolates were tested for their susceptibility to seven antipseudomonal drugs via disc diffusion AST, phenotypic detection of ESBL via double disc synergy test (DDST), and plasmid extraction on twenty isolates based on their resistance to two or more classes of antibiotics via alkaline lysis and analysis using Lambda DNA/Hind lll marker. In the overall assay, piperacillin-tazobactam and imipenem had the highest susceptibilities, whereas ceftazidime and carbenicillin had the highest resistances. 15 of 100 isolates 10 vegetable, 3 clinical, and 2 poultry—showed synergy with the beta-lactamase inhibitor, demonstrating ESBL generation by DDST. Plant, poultry, cow, and clinical isolates have plasmids. 6 strains contained 1 plasmid, 5 had 2–4, and 1 had 5. Plasmids are 1–25kbp. ESBL and Plasmids in the isolates reveal diverse resistance mechanisms. Multiple-resistance P. aeruginosa isolates in plants and animals are a public health risk. 6 strains contained 1 plasmid, 5 had 2–4, and 1 had 5. Plasmids are 1–25kbp. ESBL and Plasmids in the isolates reveal diverse resistance mechanisms. Multiple-resistance P. aeruginosa isolates in plants and animals are a public health risk.