Enterococcus spp. are significant pathogens in immunocompromised hosts, often causing severe infections due to their ability to resist antibiotics and evade immune responses. These bacteria, normally part of the gut microbiota, can become opportunistic pathogens in individuals with weakened immune systems. The review highlights the challenges in treating Enterococcus infections, including antibiotic resistance and the difficulty of resolving infections due to impaired immune responses. Risk factors such as prior antibiotic use, medical device insertion, and prolonged hospitalization contribute to Enterococcus overgrowth and resistance. The review summarizes current knowledge on virulence factors, antimicrobial resistance mechanisms, and host-pathogen interactions. It emphasizes the need for further research to better understand and manage enterococcal infections in immunocompromised patients. The review also discusses the epidemiology of Enterococcus infections, noting variations in resistance rates across different regions and the increasing prevalence of multidrug-resistant strains. Molecular epidemiology studies reveal the genetic diversity of Enterococcus species, with hospital-adapted strains showing higher resistance. Clinical impact includes a range of infections such as bacteraemia, endocarditis, and intra-abdominal infections, with high mortality rates in immunocompromised individuals. Antimicrobial resistance mechanisms, including vancomycin resistance, pose significant challenges in treatment. Virulence factors such as biofilm formation, adhesion, and toxin production contribute to the pathogenicity of Enterococcus. The review also addresses the interactions between Enterococcus and immunocompromised hosts, highlighting the role of immune system dysfunction in susceptibility. Therapeutic approaches for susceptible Enterococcus strains include combinations of beta-lactam and aminoglycoside antibiotics, while VRE infections require alternative treatments due to resistance. Prevention strategies involve infection control measures, environmental cleaning, and antimicrobial stewardship to reduce the spread of resistant strains. The review underscores the importance of surveillance, early detection, and targeted interventions to manage Enterococcus infections in high-risk populations. Overall, the review emphasizes the need for continued research and improved strategies to combat Enterococcus infections in immunocompromised individuals.Enterococcus spp. are significant pathogens in immunocompromised hosts, often causing severe infections due to their ability to resist antibiotics and evade immune responses. These bacteria, normally part of the gut microbiota, can become opportunistic pathogens in individuals with weakened immune systems. The review highlights the challenges in treating Enterococcus infections, including antibiotic resistance and the difficulty of resolving infections due to impaired immune responses. Risk factors such as prior antibiotic use, medical device insertion, and prolonged hospitalization contribute to Enterococcus overgrowth and resistance. The review summarizes current knowledge on virulence factors, antimicrobial resistance mechanisms, and host-pathogen interactions. It emphasizes the need for further research to better understand and manage enterococcal infections in immunocompromised patients. The review also discusses the epidemiology of Enterococcus infections, noting variations in resistance rates across different regions and the increasing prevalence of multidrug-resistant strains. Molecular epidemiology studies reveal the genetic diversity of Enterococcus species, with hospital-adapted strains showing higher resistance. Clinical impact includes a range of infections such as bacteraemia, endocarditis, and intra-abdominal infections, with high mortality rates in immunocompromised individuals. Antimicrobial resistance mechanisms, including vancomycin resistance, pose significant challenges in treatment. Virulence factors such as biofilm formation, adhesion, and toxin production contribute to the pathogenicity of Enterococcus. The review also addresses the interactions between Enterococcus and immunocompromised hosts, highlighting the role of immune system dysfunction in susceptibility. Therapeutic approaches for susceptible Enterococcus strains include combinations of beta-lactam and aminoglycoside antibiotics, while VRE infections require alternative treatments due to resistance. Prevention strategies involve infection control measures, environmental cleaning, and antimicrobial stewardship to reduce the spread of resistant strains. The review underscores the importance of surveillance, early detection, and targeted interventions to manage Enterococcus infections in high-risk populations. Overall, the review emphasizes the need for continued research and improved strategies to combat Enterococcus infections in immunocompromised individuals.