Existing software tools for topology-based pathway enrichment analysis are either computationally inefficient, have undesirable statistical power, or require expert knowledge to leverage the methods’ capabilities. To address these limitations, we have overhauled NetGSA, an existing topology-based method, to provide a computationally-efficient user-friendly tool that offers interactive visualization. Pathway enrichment analysis for thousands of genes can be performed in minutes on a personal computer without sacrificing statistical power. The new software also removes the need for expert knowledge by directly curating gene-gene interaction information from multiple external databases. Lastly, by utilizing the capabilities of Cytoscape, the new software also offers interactive and intuitive network visualization.