<p>The design of polymer-carbon nanocomposites with enhanced adsorption efficiency for emerging contaminants is critical for sustainable water remediation. Graphene-polymer composites are increasingly explored for their potential in the adsorption of organic material, but the molecular mechanisms governing the adsorption and interfacial miscibility remain poorly understood. This study used a multiscale computational framework, integrating quantum and all–atom molecular dynamics simulations with a thermodynamic Flory-Huggins free energy of mixing analysis to elucidate adsorption energetics and the bulk thermodynamic miscibility of graphene oxide (GO)/polyvinyl alcohol (PVA) composites with pharmaceuticals. This multiscale approach provided a prediction of adsorbent–adsorbate interactions consistent with experimental trend-based observation, validating GO–PVA as an efficient hybrid matrix for pharmaceutical adsorption, with the adsorption strength strongly dependent on the molecular structure of the pollutants. The hydrogen bonding and π-π stacking interactions are the predominant binding modes, while the dominant interaction type is physisorption, though chemisorption occurred in a few high-binding-energy adsorbent-adsorbate complexes. Temperature-dependent Flory-Huggins free energy analysis indicated that GO–PVA–H₂O systems possess highly favorable mixing thermodynamics, whereas neat PVA–H₂O interactions remain unfavorable, highlighting the hydrophilic enhancement conferred by GO. The combined results suggest that GO–PVA composites not only improve water compatibility but also enhance the affinity for pharmaceutical adsorption. Among the tested drugs with consensus rankings, irbesartan and ketoprofen showed the highest affinities toward GO, PVA, and GO–PVA composites. This study provides valuable molecular-level insights supporting the use of GO–PVA composites as promising adsorbents for the removal of pharmaceuticals from aqueous environments.</p>