Background and aims <p>The relationship between serum uric acid (SUA) levels and cardiometabolic syndrome (CMS) remains controversial. This study aims to investigate the association between SUA and CMS in a large, nationally representative US population.</p> Methods <p>This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020. Logistic regression models were used to evaluate the association between SUA and CMS, while restricted cubic spline analysis explored the dose-response relationship. Subgroup analyses were conducted to examine effect modifications by demographic and socioeconomic factors.</p> Results <p>The study included 12,638 participants. After adjusting for multiple confounders, higher SUA levels were significantly associated with increased odds of CMS (OR: 1.37, 95% CI: 1.31–1.42). This association remained consistent across different SUA quartiles, with the highest quartile showing the strongest association (OR: 2.72, 95% CI: 2.34–3.16). Restricted cubic spline analysis revealed a nonlinear dose-response relationship between SUA and CMS. Subgroup analyses showed that the association was stronger in females (OR: 1.78, 95% CI: 1.69–1.87) compared to males (OR: 1.47, 95% CI: 1.41–1.54), and varied across education levels and racial/ethnic groups.</p> Conclusion <p>Our findings indicate a significant positive association between SUA levels and CMS in the US adult population. This relationship appears to be linear and is influenced by factors such as sex, education level, and race/ethnicity. These results suggest that SUA levels may be a useful marker for CMS assessment and potential intervention strategies.</p> Clinical trial number <p>Not applicable.</p>