A novel geometry-independent neutral desorption (GIND) device was successfully developed, which made neutral desorption (ND) sampling easier and more robust on virtually all types of surfaces. The GIND device features a small air-tight enclosure with fixed space between the ND gas emitter, the sample surface, and the sample collector. Besides easy fabrication and convenient use, this configuration facilitates efficient neutral sample transfer and results in high sensitivity by preventing material loss during the ND process. The effects of various operating parameters of the GIND device such as desorption gas composition, surface wetness, gas flow rate, distance between the surface and the gas emitter, internal diameter of the sample outlet, and GIND device material were experimentally investigated. By using the GIND device, trace amounts of typical explosives such as TNT, RDX, HMX, TATP, etc., were successfully sampled from many different kinds of surfaces, including human skin, glove, glass, envelope, plastic, leather, glass, and clothes. GIND-sampled explosives were detected by multiple-stage extractive electrospray ionization mass spectrometry (EESI-MS). Ion/molecule reactions of explosives such as RDX and TATP were implemented in the EESI source for the rapid detection with enhanced sensitivity and specificity. The typical time for a single sample analysis was a few seconds. Successful transportation of the neutral analytes over a distance longer than 10 m was demonstrated, without either significant signal loss or serious delay of signal response. The limit of detection for these explosives in the study was in the range of ca. 59–842 fg (S/N = 3, n = 8) on various surfaces. Acceptable relative standard deviation (RSD) values (ca. 4.6–10.2%, n = 8) were obtained for all the surfaces tested, showing the successful sampling of trace non-volatile explosive compounds (sub-picogram) by the GIND device for the EESI mass spectrometric analysis.