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In this study, we developed an integration of numerical computations with a theoretical modeling framework that couples three phase viscous-laminar transient simulations of glycocalyx-patched tumor vessel resolving plasma, red blood cells (RBCs), and white blood cells (WBCs) and tracking their volume fractions to a calibrated reverse advection-diffusion (RAD) model for intratumoral plasma transport. The reduced-order tumor microenvironment model uses histology-informed extracellular matrix (ECM) tumor domain and packing fraction, together with explicit glycocalyx-patch electrohydrodynamics (EHD) at the tumor vessel wall. At the fenestra, EHD increases inlet plasma intensity relative to a non-EHD framework across all models (means: 0.576 non-EHD vs 0.722 EHD; gain 25.34%). Numerical simulations of plasma perfusion in both the tumor ECM domain and a microfluidic benchmark exhibit two-stage kinetics, with an initial advection-dominated regime. The RAD model reproduces this behavior and, after a simple temporal calibration to account for pore-scale hydrodynamic acceleration resolved by computational fluid dynamics (CFD), matches the observed propagation. By using fully resolved, EHD-inclusive multiphase CFD simulations to calibrate a reduced-order RAD model parameterized by measurable geometric features, we bridge the gap between classical Darcy\u2013Starling tissue perfusion models and fully resolved CFD. The resulting framework provides a tractable, mechanism-grounded tool for quantifying plasma progression in dense solid tumors.<\/jats:p>","DOI":"10.1101\/2025.11.15.688588","type":"posted-content","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T17:10:17Z","timestamp":1763399417000},"source":"Crossref","is-referenced-by-count":0,"title":["Reduced-order modeling of solute transport within physiologically realistic solid tumor microenvironment"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-0531","authenticated-orcid":false,"given":"Mohammad Mehedi Hasan","family":"Akash","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Yeasin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shima","family":"Mahmoudirad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Redowan A","family":"Niloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyan","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Reindl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupum","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1464-8425","authenticated-orcid":false,"given":"Saikat","family":"Basu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025112004251541000_2025.11.15.688588v1.1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000386057","article-title":"Tumor pathophysiology: the perfusion model","volume":"28","year":"1980","journal-title":"Antibiotics and Chemotherapy"},{"issue":"1","key":"2025112004251541000_2025.11.15.688588v1.2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1754-1611-8-12","article-title":"Effect of tumor shape, size, and tissue transport properties on drug delivery to solid tumors","volume":"8","year":"2014","journal-title":"Journal of biological engineering"},{"key":"2025112004251541000_2025.11.15.688588v1.3","doi-asserted-by":"crossref","unstructured":"Vaupel, P.and Kallinowski , F. and Okunieff, P. 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