Severe sepsis causes organ dysfunction and continues to be the leading reason for pediatric death worldwide. Early recognition of sepsis could substantially promote precision treatment and reduce the risk of pediatric death. The host cellular response to infection during sepsis between adults and pediatrics could be significantly different. A growing body of studies focused on finding markers in pediatric sepsis in recent years using multi‐omics approaches. This narrative review summarized the progress in studying pediatric sepsis biomarkers from genome, transcript, protein, and metabolite levels according to the omics technique that has been applied for biomarker screening. It is most likely not a single biomarker could work for precision diagnosis of sepsis, but a panel of markers and probably a combination of markers detected at multi‐levels. Importantly, we emphasize the importance of group distinction of infectious agents in sepsis patients for biomarker identification, because the host response to infection of bacteria, virus, or fungus could be substantially different and thus the results of biomarker screening. Further studies on the investigation of sepsis biomarkers that were caused by a specific group of infectious agents should be encouraged in the future, which will better improve the clinical execution of personalized medicine for pediatric sepsis.