The co-gasification of coal and biomass offers numerous benefits, including improved gasification efficiency, reduced pollution emissions, and the utilization of renewable resources. However, there is a lack of comprehensive research on the synergistic effects of, and influence parameters on, coal−biomass co-gasification. This study employs Aspen Plus simulations to investigate the co-gasification behavior of coal and corn straw, focusing on the synergistic effects and the impact of various operating conditions. A synergistic coefficient is defined to quantify the interactions between the feedstocks. Sensitivity analyses explore the effects of gasification temperature (800−1300 °C), coal rank (lignite, bituminous, anthracite), biomass mass fraction (0−50%), oxygen-to-carbon ratio, and steam-to-carbon ratio on the synergistic coefficients of effective syngas content (CO + H2), specific oxygen consumption, specific fuel consumption, and cold gas efficiency. The results reveal an optimal biomass mass fraction of 10% for maximizing cold gas efficiency, with the syngas primarily consisting of H2 (36.8%) and CO (61.6%). Higher gasification temperatures (up to 1200 °C) improve syngas quality and process efficiency, while higher-rank coals exhibit better gasification performance compared to lignite. Optimal oxygen-to-carbon and steam-to-carbon ratios are identified for maximizing syngas yield and quality. These findings provide valuable guidance for the design and optimization of industrial coal−biomass co-gasification processes, enabling the maximization of syngas quality, process efficiency, and resource utilization.