In this work, sodium alginate (NaAlg) membranes were enhanced with synthesized zinc oxide (ZnO) nanoplates to enable efficient pervaporation dehydration of isopropyl alcohol (IPA). A comprehensive suite of characterisation techniques—scanning electron (SEM) and atomic force (AFM) microscopy, Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), contact angle and liquid uptake measurements—along with density functional theory (DFT) calculations, was employed to establish robust structure–property relationships and to elucidate filler–polymer interactions. Membranes with different ZnO contents were prepared, and membranes based on the optimal NaAlg-ZnO(5%) composite were cross-linked with CaCl2 to improve stability in aqueous solutions, and supported membranes were developed for prospective applications by applying this composite onto the prepared porous cellulose acetate (CA) substrate. This developed cross-linked supported NaAlg-ZnO(5%)/CA membrane had a permeation flux increased by 2 times or more compared to a dense NaAlg membrane during dehydration of IPA (12–30 wt.% water) with a permeate water content above 99 wt.%. The integrated experimental–theoretical approach provides mechanistic insight into ZnO–NaAlg interactions and demonstrates the strong potential of these mixed matrix membranes for high-efficiency alcohol dehydration, offering a rational design paradigm for next-generation pervaporation membranes.