The transportation sector's need for new fuels is being addressed through the development of optimization methods, and the use of combined and alternative fuels, which will prove to be both efficient and cost-effective. This paper utilizes a multi-criteria approach, including the response surface method and Taguchi method, to evaluate several alternative fuels for a heavy-duty diesel engine. The study considers a midterm horizon to address the issue of the near future. For this purpose, the economic effects and optimization of a natural gas and diesel fuel combination were evaluated. The optimization results showed that the engine operated best at a constant speed of 1400 rpm. The results indicate that when modeling combustion emissions with RSM, the effects of CO and NOx must be considered. When determining the optimal level of variables, it is important to increase the interval between the compression ratio and the start time of fuel injection until a specific level of emission reduction is achieved. Furthermore, Taguchi method has demonstrated that the impact of alterations in gas fuel and injection start time on the modeling of emission and performance parameters is more significant than that of other variables. The TOPSIS method was used to determine the economic, functional, and emission performance of different engine operation processes, it was found that the economic and functional criteria were aligned. However, the best solution for the environmental criterion was to focus on management.