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The current study deals with the design of ultra-high molecular weight polyethylene (UHMWPE) composites by integrating various micro and nanoparticles as reinforcements for enhanced performance of acetabular cups in hip prostheses. For the design, a data-driven design approach was implemented, exploiting natural computing techniques such as Artificial Neural Network (ANN) and Genetic Algorithm (GA). Experimental data related to UHMWPE reinforced with carbon nanotube, graphene, carbon fiber, and hydroxyapatite were gathered from the published works of previous researchers. To study the relationship between the volume fraction and the morphology of the particles with the tribological and mechanical properties of the composites, ANN modeling and sensitivity analyses were used. Optimization of the properties was done with the developed ANN models as objective functions in order to find the optimal combinations of reinforcements, which helps to achieve enhanced tribo-mechanical properties of the composites. This natural computing approach of designing the UHMWPE composites paved a way for experimentation.