Advanced hemodialysis therapies, such as online hemodiafiltration (OL-HDF), aim to improve the removal of both water-soluble waste products and protein-bound uremic toxins (PBUTs), which are poorly cleared by conventional hemodialysis. Mathematical models are increasingly used to describe solute kinetics and optimize treatment performance; however, most proposed mechanistic approaches still rely on population-averaged parameters, thereby limiting their predictive accuracy at the individual level. Concurrently, computational fluid dynamics (CFD) offers the potential to provide a more detailed representation of transport phenomena within hemodialyzers. However, its application remains limited due to the complexity of accurately modeling fluid flow and mass transport in hollow-fiber membrane bundles while maintaining a reasonable computational cost.