This study presents an integrated approach that combines the Levenberg–Marquardt (LM) and Luus–Jaakola (LJ) algorithms to enhance parameter estimation for various applications. The LM algorithm, known for its precision in solving non-linear least squares problems, is effectively paired with the LJ algorithm, a robust stochastic optimization method, to improve accuracy and computational efficiency. This hybrid LM-LJ methodology is demonstrated through several case studies, including the optimization of MESH equations in distillation processes, modeling controlled diffusion in biopolymer films, and analyzing heat and mass transfer during the drying of cylindrical quince slices. By overcoming the convergence issues typical of gradient-based methods and performing global searches without initial parameter bounds, this approach effectively handles complex models and closely aligns simulation results with experimental data. These capabilities highlight the versatility of this approach in engineering and environmental modeling, significantly enhancing parameter estimation in systems governed by differential equations.