Currently, conventional spark–ignition engines face challenges in meeting the ever-growing demands of customers and increasingly stringent regulations regarding pollutant emissions. A combination of innovative strategies and carbon-neutral fuels is deemed necessary in order to further reduce fuel consumption and minimize engine emissions. The present work aims to assess the performance of combustion strategies using low-carbon-content fuel, such as methanol M100, ignited by a plasma-assisted igniter (PAI) under ultra-lean conditions. The experimental campaign is conducted on a single-cylinder research engine at 1000 rpm and low loads, moving up to the engine lean stable limits. The specific purpose of this work is to determine the benefits brought by the proposed strategy, referred to as M100–PAI, which compared market gasoline E5 ignited by the PAI system and conventional spark. The synergy between M100 (methanol) and Plasma-Assisted Ignition (PAI) in internal combustion engines yielded notable benefits. This combination significantly improved combustion stability if compared to the other combinations tested, by extending the lean stable limit to λ = 2.0, reducing cycle-to-cycle variability, and facilitating faster flame front acceleration, resulting in enhanced homogeneity. These enhancements, obtained with the combination M100–PAI, contributed to higher fuel efficiency, showing a 10% efficiency gain over the combination E5–gasoline spark ignition. The findings highlight the potential of innovative combustion strategies using low-carbon fuels and advanced ignition systems to meet stringent emissions regulations while improving engine performance.