Comprehensive analysis of organic compounds is crucial yet challenging considering that information on elements, fragments, and molecules is unavailable simultaneously by current analytical techniques. Additionally, many compounds are insoluble or only dissolve in toxic solvents. A solvent- and matrix-free strategy has been developed which allows the organic compound analyzed in its original form. It utilizes thermal diffusion desorption with the solid analyte irradiated with high energy laser. It is capable of providing explicit elemental, fragmental, and molecular information simultaneously for a variety of organic compounds. Thermal diffusion desorption has many advantages compared to the electrospray and MALDI techniques. The protons that form the protonated molecular ions originate from the analyte itself. All the elements and fragments are also derived from the analyte itself, which provides abundant information and expedites the identification of organic compounds.