Abstract Today, nanotechnology has generated an increase in the design of new nanomaterials that cut across biological barriers for application in the human body. On the other hand, the application of quantum chemistry models allow modeling, predicting, and designing new nanomaterials with specific properties and structure for specific applications due to manipulation of nanoscale materials. In this investigation, the crosslinking of the PU/graphene nanocomposite (NMC) applied AM1 model was studied, in which graphene was introduced in order to improve the properties of PU and its wide medical application, then the minimum amount was determined for PMMA absorption in the NMC. By applying the Monte Carlo method, the effect of temperature (273, 308, 310, and 313K, respectively) was studied to determine the behavior of NMC/PMMA in the prosthetic design. Calculations were: (1) molecular geometry whereby regarding Gibbs free energy (ΔG) minimal changes of 0.1% with respect to different temperatures was observed; (2) The partition coefficient (Log P) shows a positive value (24.77), which would verify that this reaction with polar solutions in the human body; (3) the main signals FTIR about the NMC/PMMA, where it is seen that the temperature only causes displacements in the different signals; it was observed that the crosslinking of the PU/graphene occurs in the carbonyl bonds and CH forming hydrogen bonds and PMMA is added when the adsorption is carried out through the CH-graphene; (4) electrostatic potential maps (MESP) of the NMC/PMMA at different temperatures shows that the nucleophilic zones (CH bonds) identified bonds, while electrophilic zones were located in the carbonyl group. These results verify that the prosthesis has excellent physicochemical properties independent of changes in body temperature.