This paper reports an investigation of a highly stratified methanol direct injection spark ignition (DISI) engine with a high compression ratio. The effects of the start of injection (SOI), spray-included angle, injection pressure, and spark timing (ST) on in-cylinder flow, fuel distribution, flame propagation, and engine performance are evaluated in detail. The combustion process of methanol DISI engine is very sensitive to the variation of SOI, which is closely associated with the in-cylinder turbulence and the fuel/air mixing. It is found that retarding SOI shows the similar effects on combustion process as reducing spray-included angle, which indicates that the effects of SOI are more related to the spray target (i.e., fuel distribution). The injection pressure affects the combustion process mainly through the impact on the fuel distribution in the cylinder. The flame propagates from the spark plug towards the cylinder axis along the in-cylinder swirl direction, and more fuel mass in the piston bowl promotes the flame propagation. Thus, more retarded SOI, smaller spray-included angle, and lower injection pressure are suggested at low loads to enrich the fuel concentration in the bowl to achieve a stable combustion. Under medium load, indicated thermal efficiency (ITE), peak pressure rise rate (PPRR), and nitrogen oxides (NOx) emissions can be improved with advanced SOI. ITE can also be improved by advancing ST with a slight penalty on PPRR and NOx. This study demonstrates the potential of simultaneously optimizing fuel injection and ST to improve engine performance.