Pediatric sepsis is a complex syndrome shaped by developmental considerations, age-specific physiology, immunologic heterogeneity, and hyperinflammatory overlap syndromes. Recent evidence underscores a dynamic interplay between hyperinflammation and immunoparalysis in pediatric patients with sepsis, emphasizing the need for rapid, personalized diagnostic tools. While revised pediatric scoring systems and targeted immunotherapies have been developed, significant knowledge gaps remain regarding optimal timing and patient selection for immunomodulatory interventions. This article consolidates current understanding of pediatric sepsis pathobiology, explores emerging pediatric subphenotypes, and examines early stage clinical trials investigating precision medicine approaches in pediatric sepsis.