Background <p>This study aimed to characterize the interplay of metabolic, hormonal, and inflammatory factors in precocious puberty and obesity.</p> Methods <p>This cross-sectional study enrolled 417 children were included Control (<i>n</i> = 97), Obesity (<i>n</i> = 102), Central Precocious Puberty (CPP, <i>n</i> = 103), and obesity with precocious puberty group (OPP, <i>n</i> = 115) groups. Basic anthropometric, hormonal, metabolic, and inflammatory indicators were analyzed. Group comparisons were performed using ANOVA/Kruskal-Wallis tests. Receiver operating characteristic (ROC) curve was applied to assess biomarkers for predicting precocious puberty in obese children, and Spearman correlation evaluated biomarker relationships.</p> Results <p>Bone age advancement and elevated levels of LH, FSH, and IGF-1 were observed in both the CPP and OPP group compared to the Controls. ROC curve indicated that IGF-1 had high predictive value (AUC = 0.810) for precocious puberty in obese children. The Obesity and OPP groups exhibited significantly elevated triglycerides, liver enzymes (GGT, ALT), and inflammatory indices (NLR, WBC) relative to the CPP group. OPP correlated positively with LH, FSH, TC, NLR, and IGF-1.</p> Conclusion <p>Obesity-associated precocious puberty involves concurrent elevations in hormonal, metabolic, and inflammatory biomarkers. Clinical management of pubertal disorders in children with obesity should incorporate integrated assessment of inflammatory and metabolic dysregulation alongside endocrine markers.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>It provides comparative evidence that the obesity-associated precocious puberty exhibits a more severe metabolic and inflammatory profile than the Central Precocious Puberty without obesity, suggesting obesity exacerbates these dysregulations alongside puberty timing.</p> </ItemContent> <ItemContent> <p>The findings strongly argue that clinical management of precocious puberty in obese children requires an integrated approach, assessing not just hormonal markers but also metabolic health and inflammation for comprehensive evaluation.</p> </ItemContent> <ItemContent> <p>It underscores the complex interplay and potential shared mechanisms between metabolic dysfunction, inflammation, and the hormonal activation of puberty, emphasizing the need for future research to investigate these interconnected pathways in pediatric endocrine disorders.</p> </ItemContent> </UnorderedList></p>