Many observational epidemiological studies have reported an association between matrix metalloproteinases (MMPs) and urologic cancers. However, the causal relationship between these two phenotypes remains uncertain. This study aims to examine the bidirectional causal relationship between serum MMPs and three urologic cancers: kidney, prostate, and bladder cancer. Using data from large-scale genome-wide association studies (GWAS), we employed two-sample Mendelian randomization (MR) methods to assess the causal relationship between serum MMPs and urologic cancers. We performed inverse variance-weighted MR as the primary method for calculating the overall effects of multiple instruments, while implementing additional MR methods and sensitivity analyses. Odds ratios (ORs) were employed to evaluate the causal relationship between serum MMPs and urologic cancers risk. Our findings indicated a causal relationship between serum MMP-3 levels and prostate cancer risk (OR = 1.07, 95% confidence interval [CI] = [1.02, 1.11],