Articular cartilage degeneration resulting from osteoarthritis, trauma, and age-related disorders is a major cause of disability worldwide. Although total joint replacement (TJR) remains the standard treatment for advanced joint degeneration, it is associated with long-term complications such as implant loosening, stress shielding, bone necrosis, wear debris, and the need for revision surgery. These limitations arise primarily because conventional implant materials fail to replicate the unique tribological and mechanical characteristics of natural cartilage. This research explores advanced biomaterials capable of functioning as cartilage substitutes, thereby reducing the extent of surgical intervention while restoring near-natural joint performance. The study investigates the tribological and nanomechanical behaviour of polymer composites and coated refractory metals with established biocompatibility. Experimental evaluation was carried out under simulated physiological conditions using lubricants formulated to mimic natural synovial fluid. Particular emphasis was placed on reproducing the complex lubrication mechanisms—boundary, elasto-hydrodynamic, boosted, and weeping lubrication—that enable healthy synovial joints to achieve an exceptionally low coefficient of friction (~0.01). Friction, wear resistance, and surface integrity were systematically assessed to determine the suitability of the candidate materials for cartilage replacement applications. The investigations identified both favourable and limiting characteristics of the tested materials. However, optimization through microstructural modification and the use of appropriate synthetic lubricants resulted in significant improvements in tribological performance. These findings demonstrate that engineering the surface characteristics and microstructure of biocompatible materials can substantially enhance their functional behaviour under physiological loading conditions.