The transportation sector stands at the forefront of global challenges, where its significant contribution to greenhouse gas emissions and air pollution has become an urgent matter demanding immediate attention. For addressing these compelling concerns and leading the automotive industry toward a sustainable future, it is, therefore, imperative to explore the realm of alternative fuel that can effectively mitigate the environmental impact of automobiles. Methanol, a renewable alternative fuel, has gathered quite an attention due to its potential to be used as a wonderful alternative to neat gasoline in spark ignition engines. However, there are some core challenges that must be addressed to utilize methanol on a commercial scale in the transport sector. These core challenges include cold start issues, enhanced NOx emissions, 100% methanol utilization, transportation concerns and lubricant oil deterioration. In this chapter, these challenges along with their potential solutions have been discussed in detail. Moreover, different techniques such as artificial neural network and response surface methodology have been discussed to predict and optimize the usage of methanol in SI engines. The adoption of methanol, as an alternative to gasoline, will help us achieve some important sustainable development goals, thus fulfilling the promise of a sustainable future for the upcoming world.