For numerous years, PVC and aluminum doors and windows have been integral components of buildings. The primary technical requisites for doors and windows encompass superior acoustic performance, thermal insulation, and effective sealing. Particularly, the sealing properties, crucially important, are ensured by the gaskets fitted onto the profiles. This paper aims to present a gasket design with a new methodology that includes a systematic modeling-optimization process based on multiple non-linear neuro-regression. Comprehensive research has been done by multiple non-linear neuro-regression analyses of gaskets due to deficient studies in the literature on hyperelastic materials. 17 candidate functional forms based on four basic mathematical structures (polynomial, trigonometric, logarithmic, and linear functions, and their hybrid or rational forms) have been proposed to model the FEM data of the gasket. Hybrid versions of three stochastic search algorithms, Differential Evolution, Random Search, and Simulated Annealing, are considered to solve highly non-linear, non-convex, multi-variables mixed continuous-discrete problems. The experimental results were compared with the numerical result using the finite-element analysis (FEA). Nonlinear static analyses were performed with Abaqus. Stress and logarithmic strain distributions are obtained. A good correlation was found between the experimental and the numerical results The optimum locations and numbers of the nodes have been found to obtain the minimum overflow distance and the maximum compression surface area for gaskets having the same topological structure.