Sepsis-associated acute kidney injury (SA-AKI) is a critical complication of sepsis, affecting up to 70% of AKI cases. It is classified into early (within 48 hours of sepsis) and late (48 hours to 7 days after sepsis onset) based on timing. SA-AKI is associated with worse outcomes compared to sepsis or AKI alone. The pathogenesis involves multiple mechanisms, including inflammation, metabolic reprogramming, various forms of cell death (apoptosis, necroptosis, pyroptosis, ferroptosis), autophagy, efferocytosis, and hemodynamic changes. These processes contribute to renal dysfunction and injury. Biomarkers such as cystatin C, proenkephalin A, interleukins, osteoprotegerin, galectin-3, presepsin, and urinary markers like KIM-1, NGAL, and L-FABP are being explored for early detection and prognosis. Advanced technologies, including multi-omics and machine learning, are providing new insights into the molecular mechanisms of SA-AKI. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are emerging as potential therapeutic targets. Prevention strategies include timely antibiotic administration, source control of infection, and maintaining adequate MAP. Treatment involves fluid resuscitation, vasopressors, and kidney replacement therapy (KRT) when necessary. The timing and type of KRT remain debated, with early vs. late initiation being a topic of ongoing research. Therapeutic approaches include targeting autophagy, inflammation, and specific cell death pathways. Potential therapies include compounds like polydatin, alpha-lipoic acid, and Tregs, which may improve renal function and reduce injury. Future research aims to refine the classification of SA-AKI sub-phenotypes and integrate multi-omics data to develop personalized treatment strategies. The integration of omics technologies is expected to enhance the understanding of SA-AKI pathogenesis and improve diagnostic and therapeutic approaches. Overall, SA-AKI remains a complex condition requiring further investigation to optimize management and outcomes.Sepsis-associated acute kidney injury (SA-AKI) is a critical complication of sepsis, affecting up to 70% of AKI cases. It is classified into early (within 48 hours of sepsis) and late (48 hours to 7 days after sepsis onset) based on timing. SA-AKI is associated with worse outcomes compared to sepsis or AKI alone. The pathogenesis involves multiple mechanisms, including inflammation, metabolic reprogramming, various forms of cell death (apoptosis, necroptosis, pyroptosis, ferroptosis), autophagy, efferocytosis, and hemodynamic changes. These processes contribute to renal dysfunction and injury. Biomarkers such as cystatin C, proenkephalin A, interleukins, osteoprotegerin, galectin-3, presepsin, and urinary markers like KIM-1, NGAL, and L-FABP are being explored for early detection and prognosis. Advanced technologies, including multi-omics and machine learning, are providing new insights into the molecular mechanisms of SA-AKI. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are emerging as potential therapeutic targets. Prevention strategies include timely antibiotic administration, source control of infection, and maintaining adequate MAP. Treatment involves fluid resuscitation, vasopressors, and kidney replacement therapy (KRT) when necessary. The timing and type of KRT remain debated, with early vs. late initiation being a topic of ongoing research. Therapeutic approaches include targeting autophagy, inflammation, and specific cell death pathways. Potential therapies include compounds like polydatin, alpha-lipoic acid, and Tregs, which may improve renal function and reduce injury. Future research aims to refine the classification of SA-AKI sub-phenotypes and integrate multi-omics data to develop personalized treatment strategies. The integration of omics technologies is expected to enhance the understanding of SA-AKI pathogenesis and improve diagnostic and therapeutic approaches. Overall, SA-AKI remains a complex condition requiring further investigation to optimize management and outcomes.