Background: Sepsis is a time critical syndrome were delays in recognition and antimicrobial delivery increase morbidity and mortality. The expansion of prehospital services, electronic health records, point-of care testing, and host-response biomarkers has created opportunities for earlier detection and better risk stratification in the care continuum. Objective: To synthesize evidence on multimodal strategies combining prehospital assessment, digital early warning systems, conventional laboratory markers, and host-response assays for early sepsis detection and clinical outcome improvement. Methods: We conducted a systematic review of original studies evaluating diagnostic or early warning approaches for suspected sepsis from prehospital care to emergency department and inpatient settings. We searched major electronic databases and screened records using predefined eligibility criteria. Data were extracted on study design, setting, sample size, index strategy, comparators, and outcomes. Results: Seven eligible studies were included. Evidence suggests that adding prehospital lactate improves identification of higher mortality risk even when triage scores appear low. Machine learning tools using vital signs and EHR data demonstrated strong discrimination for sepsis-related outcomes and, in some settings, were associated with faster antibiotic administration and improved survival. A rapid host-response assay showed potential to distinguish sepsis from non-infectious inflammation within clinically actionable timeframes. Conclusion: Multimodal integration of prehospital biomarkers, digital alerts, and host-response diagnostics appears promising for earlier recognition and improved sepsis care. More pragmatic trials and implementation studies are needed.