Pseudomonas aeruginosa is an opportunistic pathogen with a multidrug-resistant profile that has become a critical threat to global public health. It is one of the leading causes of severe healthcare-associated infections, including ventilator-associated pneumonia, chronic infections in patients with cystic fibrosis, and bloodstream infections in immunosuppressed individuals. The development of vaccines against P. aeruginosa represents a major challenge due to the high capacity of this bacterium to form biofilms, its broad arsenal of virulence factors, and its ability to evade the host immune system. Producing a successful vaccine against P. aeruginosa may be possible in the near future through the use of multivalent strategies, including advanced technologies such as nanotechnology and RNA-based platforms, and by acquiring more detailed knowledge regarding host-pathogen interactions.