The article provides a comprehensive review of *Enterococcus* spp. infections in immunocompromised hosts, highlighting their virulence, antimicrobial resistance, and host-pathogen interactions. *Enterococcus* spp., particularly *E. faecalis* and *E. faecium*, are significant pathogens in healthcare settings due to their ability to cause severe infections and their resistance to multiple antibiotics. The review discusses the epidemiological patterns of *Enterococcus* infections, including the rise of vancomycin-resistant *Enterococcus* (VRE) and the challenges posed by multidrug-resistant (MDR) strains. It also explores the molecular epidemiology of *Enterococcus* species, emphasizing the role of population genetics studies in understanding their evolutionary dynamics. The clinical impact of *Enterococcus* infections is discussed, focusing on the high morbidity and mortality rates associated with these infections, especially in immunocompromised patients. The article delves into the mechanisms of antimicrobial resistance, such as the acquisition of *van* genes and the production of β-lactamases, and the challenges in treating VRE infections. Additionally, it examines the virulence factors of *Enterococcus* spp., including their ability to form biofilms and their interaction with host cells. The review concludes with therapeutic approaches and prevention strategies, emphasizing the need for enhanced surveillance, infection control measures, and the development of new antimicrobial agents to combat *Enterococcus* infections.The article provides a comprehensive review of *Enterococcus* spp. infections in immunocompromised hosts, highlighting their virulence, antimicrobial resistance, and host-pathogen interactions. *Enterococcus* spp., particularly *E. faecalis* and *E. faecium*, are significant pathogens in healthcare settings due to their ability to cause severe infections and their resistance to multiple antibiotics. The review discusses the epidemiological patterns of *Enterococcus* infections, including the rise of vancomycin-resistant *Enterococcus* (VRE) and the challenges posed by multidrug-resistant (MDR) strains. It also explores the molecular epidemiology of *Enterococcus* species, emphasizing the role of population genetics studies in understanding their evolutionary dynamics. The clinical impact of *Enterococcus* infections is discussed, focusing on the high morbidity and mortality rates associated with these infections, especially in immunocompromised patients. The article delves into the mechanisms of antimicrobial resistance, such as the acquisition of *van* genes and the production of β-lactamases, and the challenges in treating VRE infections. Additionally, it examines the virulence factors of *Enterococcus* spp., including their ability to form biofilms and their interaction with host cells. The review concludes with therapeutic approaches and prevention strategies, emphasizing the need for enhanced surveillance, infection control measures, and the development of new antimicrobial agents to combat *Enterococcus* infections.