Updated project metadata. Spheroid formation during epithelial ovarian cancer progression correlates with peritoneal organ colonization, disease recurrence, and poor prognosis. Although cancer progression has been demonstrated to be associated with and driven by metabolic changes within transformed cells, possible associations between metabolic dynamics and metastatic morphological transitions remain unexplored. To address this problem, performed quantitative proteomics was performed to identify protein signatures associated with three distinct morphologies (2D monolayers and two geometrically individual three-dimensional spheroidal states) of the high-grade serous ovarian cancer line OVCAR-3. Integrating the protein states into genome-scale metabolic models allowed the construction of context-specific metabolic models for each morphological stage of the OVCAR-3 cell line and systematically evaluate their metabolic functionalities.