A comprehensive investigation into the effects of nonlinear material behaviour of polymeric (MN) and skin on the dynamics of the MN insertion in skin was undertaken in this study using experiments and numerical simulations. The nonlinearity of the material behaviour was incorporated by employing the Ramberg–Osgood and neo-Hookean equations for stress–strain relationships for the MN materials and skin, respectively. For this purpose, a characteristic type of dissolving MN array was selected. This type of MN is made by a combination of poly(vinyl alcohol) and poly(vinyl pyrrolidone). The numerical simulations were validated using experimental investigations where the MNs were fabricated using laser-engineered silicone micromould templates technology. Young’s modulus, Poisson’s ratio, and compression breaking force for the MN polymers were determined using a texture analyser. The alignment between experimental findings and simulation data underscores the accuracy of the parameters determined through mechanical testing and mathematical calculations for both MN materials (PVP/PVA) and skin behaviour during the MN insertion. This study has demonstrated a strong alignment between the experimental findings and computational simulations, confirming the accuracy of the established parameters for MNs and skin interactions for modelling MN insertion behaviour in skin, providing a solid foundation for future research in this area.