Nowadays hip arthroplasty is recognized as one of the most successful orthopedic surgical procedures, even if it involves challenges to overcome, such that lately, younger and more active patients are in need of total arthroplasty. Wear is still one of the main issues affecting joint prostheses endurance, and often causes loosening accompanied by implant failures. Actual in vitro wear tests executed by mechanical simulators have a long duration, are very expensive, and do not take into account all the possible daily activities of the patients; thus, the challenge to obtain a complete in silico tribological and dynamical model of (bio) tribo-systems could give the possibility to overcome the actual testing procedures and could contribute as a tool for a more accurate tribological design of human prostheses. This prospective paper is intended to underline actual research trends toward the challenge of having accurate numerical algorithms to be used both in preclinical testing and in the optimizations of the prostheses design. With this aim we depicted the possible in silico approach in artificial joints’ wear assessment over time, accounting for contact mechanics, numerical stress–strain analysis, musculoskeletal multibody, and synovial lubrication modelling (boundary/mixed, hydrodynamic, and elastohydrodynamic).