Highlights
• Early diagnosis of necrotizing soft tissue infections (NSTIs) remains challenging because the initial clinical features overlap with those of cellulitis and other clinical mimics.
• The Laboratory Risk Indicator for Necrotizing Fasciitis and related laboratory-based scores show variable sensitivities across settings and should not delay surgical consultation when NSTIs are clinically suspected.
• Imaging (computed tomography/magnetic resonance imaging/point-of-care ultrasound) can support triage, but no single modality is definitive, especially for hemodynamically unstable intensive care unit (ICU) patients.
• Multi-omics profiling (transcriptomics, proteomics, immunomics, and metabolomics) reveals pathogen- and host-response signatures that may improve diagnostic and prognostic stratification.
• Machine learning models integrating clinical, imaging, and omics data provide a framework for personalized risk prediction and an ICU-oriented diagnostic roadmap.

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