Chronic kidney disease (CKD) remains a significant global health burden, often diagnosed at advanced stages due to the limitations of traditional biomarkers such as serum creatinine and estimated glomerular filtration rate (eGFR). This review aims to critically evaluate recent advancements in novel biomarkers, multi-omics technologies, and artificial intelligence (AI)-driven diagnostic strategies, specifically addressing existing gaps in early CKD detection and personalized patient management. We specifically explore key advancements in CKD diagnostics, focusing on emerging biomarkers-including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), soluble urokinase plasminogen activator receptor (suPAR), and cystatin C-and their clinical applications. Additionally, multi-omics approaches integrating genomics, proteomics, metabolomics, and transcriptomics are reshaping disease classification and prognosis. Artificial intelligence (AI)-driven predictive models further enhance diagnostic accuracy, enabling real-time risk assessment and treatment optimization. Despite these innovations, challenges remain in biomarker standardization, large-scale validation, and integration into clinical practice. Future research should focus on refining multi-biomarker panels, improving assay standardization, and facilitating the clinical adoption of precision-driven diagnostics. By leveraging these advancements, CKD diagnostics can transition toward earlier intervention, individualized therapy, and improved patient outcomes.