The article reviews recent advances in the development of novel therapeutic strategies against multidrug-resistant (MDR) *Pseudomonas aeruginosa*. *P. aeruginosa* is a significant opportunistic pathogen causing various infections, including those in cystic fibrosis, ventilator-associated pneumonia, urinary tract infections, and burn injuries. The high diversity and large genome of *P. aeruginosa* have led to its ability to develop various molecular mechanisms for antimicrobial resistance, such as outer membrane permeability, drug-resistant efflux pumps, and the presence of antibiotic resistance genes. The review focuses on recent findings on the regulatory interaction between peptidoglycan and lipopolysaccharide (LPS) synthesis, which provide additional clues against pathogenic *P. aeruginosa*. It explores current and emerging treatment strategies, including phage therapy, vaccines, nanoparticles, and their combinatorial therapies. Key therapeutic agents and strategies discussed include *LpxC* inhibitors, LPS modification, LPS transport, and porins. The article also highlights the challenges in developing new antibiotics and the importance of novel therapeutic strategies to combat MDR *P. aeruginosa*.The article reviews recent advances in the development of novel therapeutic strategies against multidrug-resistant (MDR) *Pseudomonas aeruginosa*. *P. aeruginosa* is a significant opportunistic pathogen causing various infections, including those in cystic fibrosis, ventilator-associated pneumonia, urinary tract infections, and burn injuries. The high diversity and large genome of *P. aeruginosa* have led to its ability to develop various molecular mechanisms for antimicrobial resistance, such as outer membrane permeability, drug-resistant efflux pumps, and the presence of antibiotic resistance genes. The review focuses on recent findings on the regulatory interaction between peptidoglycan and lipopolysaccharide (LPS) synthesis, which provide additional clues against pathogenic *P. aeruginosa*. It explores current and emerging treatment strategies, including phage therapy, vaccines, nanoparticles, and their combinatorial therapies. Key therapeutic agents and strategies discussed include *LpxC* inhibitors, LPS modification, LPS transport, and porins. The article also highlights the challenges in developing new antibiotics and the importance of novel therapeutic strategies to combat MDR *P. aeruginosa*.