Methanol is gaining traction in some regions, e.g. for road transportation in China and for marine transportation in Europe. In this research, the possibility for achieving higher power output and higher efficiency with methanol, compared to gasoline, is investigated and the influence of several engine settings, such as valve timing and intake boost control, is studied. At wide open throttle (WOT), engine speed of 1650 rpm, the brake mean effective pressure (BMEP) of the methanol-fueled engine is higher than on gasoline, by around 1.8 bar. The maximum BMEP is further increased when positive valve overlap and higher intake boost pressure are applied. Thanks to a lower residual gas fraction, and a richer in-cylinder mixture with positive valve overlap period, the engine BMEP improves by a further 2.6 bar. Because of higher volumetric efficiency with a boosted intake air, the engine BMEP enhances with 4.7 bar. The maximum BMEP for gasoline was found through a test matrix using the design of experiment approach. At that BMEP (16.3 bar), the efficiency when fueling the engine with methanol improves by 22.7% relatively with valve overlap control and by 25.75% with intake boost control. The BMEP of the methanol engine can increase to a higher value without knock when a higher boost pressure or a longer valve overlap duration is employed. Limitations are no longer engine knock, but excessive peak in-cylinder pressures, however, being over 100 bar. If the maximum pressure is limited to 100 bar, the downsizing potential with boost control is higher than with variable valve timing. The engine could be further downsized by ~10.7% with methanol by boosting the intake pressure.