This work is a novel systems biology approach to decipher the identity of specific genes and gene products involved in the advancement of colon cancer from tumorigenesis through to metastasis. Stage-based meta-analysis of tumor genome-sequencing data in public domain was conducted and multiple approaches employed for mining novel genes driving the initiation, progression and metastasis of colon cancer. The consensus stage-specific driver genes seeded the construction of ad hoc stage-specific networks, which were dissected for the centrality of genes, clustering of subnetworks, and enrichment of gene-ontology processes. Nine novel driver genes were identified as central to the initiation and tumorigenesis of colon cancer. Three, four and three novel driver genes were identified as hubs for progression to stage-II, stage-III, and stage-IV, respectively. Our results were supported by subnetwork modules and ontology analysis. Our study yielded potential diagnostic biomarkers for colon cancer as well as novel stage-specific drug targets for rational intervention. Our methodology is extendable to the analysis of other types of cancer to fill the gaps in our knowledge.