In the present study, in order to understand the overall spray combustion characteristics of DME fuel as well as to identify the distinctive differences of DME combustion processes against the conventional hydrocarbon liquid fuels, the sequence of the comparative analysis have been systematically made for DME and n-heptane liquid fuels. To realistically represent the physical processes involved in the spray combustion, this studyemploys the hybrid breakup model, the stochastic droplet tracking model, collision model, high-pressure evaporation model, and transient flamelet model with detailed chemistry. Based on numerical results, the detailed discussions are made in terms of the autoignition, spray combustion processes, flame structure, and turbulence-chemistry interaction in the n-heptane and DME fueled spray combustion processes.