<p>Bacterial infections pose a significant risk to global health, with virulence factors playing a crucial role in the development of diseases. Metalloproteases have been recognised as essential enzymes that selectively interact with and degrade vital components of the host, thus increasing vulnerability to infections. They promote breakdown of extracellular matrix proteins, including collagen, fibrin, and laminin, thereby undermining structural integrity and facilitating tissue penetration and establishment of infection. In addition to structural damage, metalloproteases interfere with immunoglobulins, antimicrobial peptides, and complement proteins, aiding pathogens in evading the host’s immune responses. To combat bacterial infections and the growing issue of antibiotic resistance, developing advanced treatments requires understanding those enzymes. By providing a comprehensive analysis of the mechanisms by which bacterial metalloproteases facilitate host–pathogen interactions, this review explores current and potential therapeutic strategies, including targeted inhibitors. For therapeutic applications, understanding virulence and immune evasion allows researchers to target bacterial metalloproteases more effectively.</p> Graphical Abstract <p></p>