AIM: To understand the molecular connectivity between the intraocular pressure (IOP) and glaucoma which will provide possible clues for biomarker candidates. METHODS: The current study uncovers the important genes connecting IOP with the core functional modules of glaucoma. An integrated analysis was performed using glaucoma and IOP microarray datasets to screen for differentially expressed genes (DEGs) in both conditions. To the selected DEGs, the protein interaction network was constructed and dissected to determine the core functional clusters of glaucoma. For the clusters, the connectivity of IOP DEGs was determined. Further, enrichment analyses were performed to assess the functional annotation and potential pathways of the crucial clusters. RESULTS: The gene expression analysis of glaucoma and IOP with normal control showed that 408 DEGs (277 glaucoma and 131 IOP genes) were discovered from two GEO datasets. The 290 DEGs of glaucoma were extended to form a network containing 1495 proteins with 9462 edges. Using ClusterONE, the network was dissected to have 12 clusters. Among them, three clusters were linked with three IOP DEGs [N-Myc and STAT Interactor (NMI), POLR3G (RNA Polymerase III Subunit G), and APAF1-interacting protein (APIP)]. In the clusters, ontology analysis revealed that RNA processing and transport, p53 class mediators resulting in cell cycle arrest, cellular response to cytokine stimulus, regulation of phosphorylation, regulation of type I interferon production, DNA deamination, and cellular response to hypoxia were significantly enriched to be implicated in the development of glaucoma. Finally, NMI, POLR3G, and APIP may have roles that were noticed altered in glaucoma and IOP conditions. CONCLUSION: Our findings could help to discover new potential biomarkers, elucidate the underlying pathophysiology, and identify new therapeutic targets for glaucoma.