In this study, thermal desorption-based ambient mass spectrometry (TDAMS) for the analysis of small organics was explored. A layer-by-layer (LBL) self-assembled multilayer of a gold nanoparticle (AuNP)-based glass chip (Glass@AuNPs) with the absorption capacity in the near-infrared (NIR) region was used as the energy absorber and as the sample holder for sample deposition at ambient condition. An NIR laser diode (808 nm) was successfully employed as the thermal desorption source to liberate only small molecules from Glass@AuNPs chips. Followed by post-ionization, the resultant ions were monitored by an ion trap mass spectrometer. Post-ionization was assisted by a spray consisting of 50% deionized water-acetonitrile containing 0.1% acetic acid generated from a short tapered capillary by employing a high voltage (4 kV). Analytes with different polarities including small acids, amino acids, insecticides, and biodiesel samples such as ethyl esters can be directly analyzed using this approach. We demonstrated that this ambient mass spectrometric method was suitable for selectively analyzing small target organics directly from complex samples without any sample pretreatment.