The unique properties of ultra-high-molecular-weight polyethylene (UHMWPE) have made composites based on this polymer the gold standard choice for articulating surfaces used in arthroplasty. However, wear debris released by prosthesis is still a major concern of the implants. In this study, we address the urgent need to revisit the current methodologies used in designing these biomaterials by fabricating UHMWPE-based nanocomposite with Hydroxyapatite (HA), Multi-walled Carbon Nanotubes (MWCNTs), and Zirconia as additives. We investigated how different combinations of these additives impact the nanocomposites' hardness, plasticity index (PI), and friction coefficient. Our results show a constant increase in hardness by increasing Zirconia. The MTT assay test and Scanning Electron Microscopy (SEM) demonstrated an increase in cell attachment and cell viability. Examining various additives' amounts, we can further explore the possibility of reaching an optimum proportion of the ingredients. Compared with other UHMWPE-based nanocomposites (UHMWPE-HA-MWCNT's), the fabricated nanocomposite shows an improvement in tribological properties.