Serous ovarian cancer (SOC) is among the most aggressive gynecological malignancies, with high mortality due to late diagnosis, therapeutic resistance, and frequent relapse. Identification of novel molecular targets and natural inhibitors is urgently needed to improve treatment outcomes. This in silico study integrated transcriptomic data to identify hub genes in SOC and evaluated phytochemicals as potential inhibitors of the prioritized target protein PSMB7 via molecular docking and ADMET analysis. A meta-analysis of three GEO datasets (GSE27651, GSE36668, GSE54388) identified differentially expressed genes using a log₂ fold-change threshold of ≥2 or ≤−2. Enrichment analysis with Enrichr revealed pathways associated with transcriptional regulation and DNA repair. A protein–protein interaction network constructed in Cytoscape and analyzed using CytoHubba, CentiScape, and MCODE identified hub genes including PSMD13, PSMC3, UBC, UBB, PSMD7, and PSMB7. Based on literature, PSMB7 was prioritized. Its crystal structure (PDB ID: 5LEL, chain A) was prepared by removing water molecules, adding hydrogens, and assigning charges. A library of phytochemicals from PubChem was energy-minimized and docked using AutoDock Vina, and ADMET properties were predicted using SwissADME and pkCSM. Withaferin A (PubChem CID: 265237) showed the strongest binding affinity (−9.265 kcal·mol⁻¹) and stable interactions in the catalytic pocket, with moderate solubility, favorable drug-likeness, and low predicted toxicity. Literature reports Withaferin A as a proteasome inhibitor capable of inducing apoptosis and cell cycle arrest, inhibiting angiogenesis and metastasis, and exerting anti-cancer effects in ovarian and other cancers. Molecular dynamics simulation over 200 ns confirmed the stability of the ligand–protein complex. Future validation will involve in vitro assays on ovarian cancer cell lines to confirm cytotoxicity, apoptosis, proteasome inhibition, and anti-metastatic effects, followed by in vivo studies in xenograft and orthotopic mouse models to assess pharmacokinetics, efficacy, and safety. These studies will provide essential experimental confirmation of Withaferin A as a natural inhibitor of PSMB7 in SOC.