Purpose&#xa0;and Objectives <p>Hydrogel-nanocarrier systems have emerged as a clinically implementable strategy to reduce glioblastoma recurrence following surgery. Despite demonstrated feasibility, the influence of intrinsic tissue and nanocarrier properties on delivery outcomes remains insufficiently understood. This study aims to quantify their individual effects on delivery performance.</p> Methods <p>A mathematical model is applied to simulate hydrogel-mediated nanocarrier delivery to the oedematous postoperative brain. Simulations are conducted in a realistic 3-D brain geometry rebuilt from medical imaging data. Nine factors are investigated, including drug release rate, nanocarrier diffusivity, blood drainage rate, partitioning at the cell membrane and within cells, drug loading dose, oedema severity, blood pressure, and tissue permeability.</p> Results <p>The modelling reveals distinct responses of delivery outcomes to each factor. Optimal ranges are identified that maximise drug availability and/or improve distribution volume and uniformity. The results suggest that drug delivery is controlled predominantly by drug release and elimination rather than transport.</p> Conclusions <p>These findings enhance understanding of the coupled interactions between drug transport and brain tissue in the post-operative environment and provide a quantitative reference for the optimisation of hydrogel-nanocarrier delivery systems to improve inhibition of glioblastoma recurrence.</p>