The main objective of this study is to prepare nanoparticles‐induced bio‐based polyurethane foam to shield electromagnetic interference (EMI) radiation in the 8–12 GHz frequency range and compare the experimental result with optimization and simulation. Polyvinylidene fluoride (PVDF), magnesium oxide (MgO), and Nickel (Ni) nanoparticles were induced into bio‐based PU (polyurethane) foam through absorption and hydrothermal reduction technique, which includes mechanical stirring, compressing, heating and evaporating. The design of experiment (DOE) methodology was used to find nanoparticle weight percentage (wt%). EMI shielding effectiveness of the bio‐based PU foam composite was measured using Vector Network Analyzer (N5230A PNA‐L). The weight percentages of the optimized sample were predicted using the response surface methodology (RSM), in which the central composite design (CCD) employed the weight percentages of the three nanoparticles as input and the results of the electromagnetic interference shielding effectiveness (EMI SE) experiment as the response output. The result from CCD showed that 3 wt% of PVDF, 10 wt% of MgO, and 1 wt% of Ni gave a maximum EMI SE of 27.78 dB. Then a confirmation sample was created for the same, and EMI SE was estimated empirically. The results obtained for the confirmation sample are 27.56 dB. Then, a scanning electron microscope image was taken for the confirmation sample to analyze nanoparticle‐induced bio‐based PU foam's structural properties. The SEM image with dxf format is imported into the radio frequency (RF) module to calculate the EMI SE through COMSOL Multiphysics. The simulated EMI SE for the confirmation sample was 25.1 dB.