Sepsis, a heterogeneous illness produced by a dysregulated host response to infection, remains a severe mortality risk. Recent discoveries in sepsis research have stressed phenotyping as a feasible strategy for tackling heterogeneity and enhancing therapy precision. Sepsis phenotyping has moved from traditional stratifications based on severity and prognosis to dynamic, phenotype-driven therapeutic options. This review covers recent progress in connecting sepsis subgroups to personalized treatments, with a focus on phenotype-based therapeutic predictions and decision-support systems. Despite ongoing challenges, such as standardizing phenotyping frameworks and incorporating findings into clinical practice, this topic has enormous promise. By investigating phenotypic variation in therapy responses, we hope to uncover new biomarkers and phenotype-driven therapeutic solutions, laying the groundwork for more effective therapies and, ultimately improving patient outcomes.Copyright © 2025 Zhang, Zhang, Zhang and Liao.