The effectiveness of established biomarkers for non-alcoholic fatty liver disease (NAFLD) within the updated framework of steatotic liver disease (SLD) remains uncertain. This cohort study examines the association of four metabolic biomarkers-retinol-binding protein 4 (RBP-4), fibroblast growth factor 21 (FGF-21), adiponectin, and osteocalcin-with SLD and its subtypes: metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction with alcohol-related liver disease (MetALD)/alcohol-related liver disease (ALD). Among 3,504 Chinese participants aged 55-70, 938 (26.8%) have developed SLD over 5 years, including 871 with MASLD and 67 with MetALD/ALD. The findings indicate that models incorporating RBP-4, FGF-21, adiponectin, and osteocalcin improve predictive accuracy for SLD beyond conventional models. Notably, adiponectin emerges as the most versatile marker, while elevated baseline levels of FGF-21 or RBP-4 indicate specific needs for metabolic or alcohol-related interventions, respectively, supporting tailored precision medicine strategies.