This study investigates the causal relationship between obesity and hyperuricemia using Mendelian Randomization (MR) and network pharmacology. The authors selected Body Mass Index (BMI) and uric acid-related single nucleotide polymorphisms (SNPs) as instrumental variables for MR analysis. Three robust analytical methods—inverse-variance weighting, weighted median, and MR-Egger regression—were used to assess the bidirectional causality. Sensitivity analysis was conducted to evaluate horizontal pleiotropy, heterogeneity, and stability. The targets related to obesity and hyperuricemia were collected and analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to explore the underlying mechanisms. The results indicate a positive causal relationship between BMI and hyperuricemia, with an odds ratio of 1.23 (95% CI: 1.11 to 1.30) for each standard deviation increase in BMI. Conversely, hyperuricemia did not influence BMI. A total of 235 intersected targets were identified, with insulin resistance being the top key target. The mechanisms between obesity and hyperuricemia involve important pathways such as adipocytokine signaling, insulin resistance, and cholesterol metabolism. The study concludes that MR analysis supports the causal association between obesity and hyperuricemia, and that obesity leads to hyperuricemia through insulin resistance, which is a critical link in the complex network pathways. This research provides theoretical support for the clinical treatment of hyperuricemia in obese patients.This study investigates the causal relationship between obesity and hyperuricemia using Mendelian Randomization (MR) and network pharmacology. The authors selected Body Mass Index (BMI) and uric acid-related single nucleotide polymorphisms (SNPs) as instrumental variables for MR analysis. Three robust analytical methods—inverse-variance weighting, weighted median, and MR-Egger regression—were used to assess the bidirectional causality. Sensitivity analysis was conducted to evaluate horizontal pleiotropy, heterogeneity, and stability. The targets related to obesity and hyperuricemia were collected and analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to explore the underlying mechanisms. The results indicate a positive causal relationship between BMI and hyperuricemia, with an odds ratio of 1.23 (95% CI: 1.11 to 1.30) for each standard deviation increase in BMI. Conversely, hyperuricemia did not influence BMI. A total of 235 intersected targets were identified, with insulin resistance being the top key target. The mechanisms between obesity and hyperuricemia involve important pathways such as adipocytokine signaling, insulin resistance, and cholesterol metabolism. The study concludes that MR analysis supports the causal association between obesity and hyperuricemia, and that obesity leads to hyperuricemia through insulin resistance, which is a critical link in the complex network pathways. This research provides theoretical support for the clinical treatment of hyperuricemia in obese patients.