Juvenile Dermatomyositis (JDM) is a rare autoimmune disease primarily affecting children, characterized by muscle weakness and skin lesions. This study identifies 145 genes significantly associated with JDM through differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), protein-protein interaction network analysis, and miRNA and transcription factor (TF) prediction, using blood and muscle microarray sequencing datasets. Functional enrichment analysis indicates that these genes are involved in crucial biological processes, including cytokine-mediated signaling, extracellular matrix organization, and immune response. Further analysis reveals key transcription factors ( e.g., STAT1, NFKB1, and IRF9) and miRNAs ( e.g., hsa-miR-127-3p, hsa-miR-17-5p, and hsa-miR-93-5p) that may regulate the expression of these critical genes in JDM. The findings provide new insights into the molecular mechanisms of JDM and offer potential targets for future diagnostic and therapeutic strategies.