This review discusses the challenges and advancements in sepsis management, emphasizing the importance of immune phenotyping and the use of modern tools like flow cytometry for personalized treatment. Sepsis, a life-threatening condition caused by systemic inflammation, leads to immune dysregulation, including lymphopenia and impaired immune function. The complexity of sepsis is due to its pathophysiology and the heterogeneity of patient responses, making it difficult to develop universally effective therapies. Phenotyping immune cells based on clinical and immunological characteristics is crucial for tailoring treatment approaches. Flow cytometry provides detailed analysis of immune cell populations and their functional states, aiding in the identification of novel biomarkers. Integrating flow cytometry with omics data, machine learning, and clinical observations can refine sepsis management, promoting personalized medicine. This approach could lead to more precise interventions, improving outcomes in sepsis patients. The review highlights the role of various immune cells, including neutrophils, monocytes, NK cells, γδ T cells, MAIT cells, and T and B lymphocytes, in sepsis pathophysiology. Sepsis induces significant changes in immune cell function, such as neutrophil dysfunction, monocyte alterations, NK cell suppression, and T and B cell impairment. These changes contribute to immune suppression and increased susceptibility to secondary infections. Metabolic shifts in immune cells, including a transition from oxidative phosphorylation to glycolysis, are also discussed. Understanding these changes is essential for developing effective therapeutic strategies in sepsis management.This review discusses the challenges and advancements in sepsis management, emphasizing the importance of immune phenotyping and the use of modern tools like flow cytometry for personalized treatment. Sepsis, a life-threatening condition caused by systemic inflammation, leads to immune dysregulation, including lymphopenia and impaired immune function. The complexity of sepsis is due to its pathophysiology and the heterogeneity of patient responses, making it difficult to develop universally effective therapies. Phenotyping immune cells based on clinical and immunological characteristics is crucial for tailoring treatment approaches. Flow cytometry provides detailed analysis of immune cell populations and their functional states, aiding in the identification of novel biomarkers. Integrating flow cytometry with omics data, machine learning, and clinical observations can refine sepsis management, promoting personalized medicine. This approach could lead to more precise interventions, improving outcomes in sepsis patients. The review highlights the role of various immune cells, including neutrophils, monocytes, NK cells, γδ T cells, MAIT cells, and T and B lymphocytes, in sepsis pathophysiology. Sepsis induces significant changes in immune cell function, such as neutrophil dysfunction, monocyte alterations, NK cell suppression, and T and B cell impairment. These changes contribute to immune suppression and increased susceptibility to secondary infections. Metabolic shifts in immune cells, including a transition from oxidative phosphorylation to glycolysis, are also discussed. Understanding these changes is essential for developing effective therapeutic strategies in sepsis management.