In this study, we have integrated the expression profiles of three major domains of cancer biology including DNA methylation, mRNA, and miRNA in healthy and Rb cancer samples using individual microarray datasets available in NCBI-GEO to comprehensively understand the epigenetic consequences of Rb loss and map the key hub and common genes that play a crucial role in the development and progression of retinoblastoma tumors. The gene discussed is RB1; the disease is retinoblastoma.