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Genomic instability has been increasingly recognized over the past decade as a fundamental driver of cancer initiation and progression, largely owing to its association with specific genes and cellular mechanisms that offer therapeutic potential. However, a comprehensive molecular framework that captures the interconnected processes underlying this phenomenon remains elusive. In this study, we focused on polo-like kinase 1 (PLK1), a key cell cycle regulator frequently overexpressed in diverse human tumors, to reconstruct a regulatory network that consolidates pre-existing biological knowledge exclusively related to pathways involved in genome stability maintenance and cancer. The resulting model integrates nine biological processes, 1030 reactions, and 716 molecular species to form a literature-supported network in which PLK1 serves as a central regulatory node. However, rather than depicting an isolated PLK1-centric system, this network reflects a broader and more complex architecture of interrelated genomic instability mechanisms. As expected, the simulations reproduced known behaviors associated with PLK1 dysregulation, reinforcing the well-established role of the kinase in genome destabilization. Importantly, this model also enables the exploration of additional, less-characterized dynamics, including the potential involvement of genes such as