Recent terrorist attacks, both in the US and abroad, have indicated that significant improvements in intelligence operations are required for adequate prevention and prosecution of terrorist acts. This includes the ability to accurately and rapidly attribute pre-detonated and post-detonated explosive devices and/or other weapons-based material to a particular source, and/or region of the world. Surface mass spectrometry methods have the potential to greatly advance the field of forensics science, allowing for simultaneous elemental, isotopic and molecular imaging on a sub-micron to nano-scale range, with superior chemical specificity and sensitivity. With recent advancements in the field of surface mass spectrometry, the versatility of these methods has increased dramatically, allowing for the direct analysis of samples at atmospheric pressure (e.g. Desorption ElectroSpray Ionization or DESI). The potential for 3-D molecular analysis in soft samples with depth resolutions on the order of 5 nm has also been realized with advent of the gas cluster ion beam (GCIB) source. Finally substantial improvements in the mass resolving power (by at least a factor of 10) has been observed when employing FT-MS mass spectrometers, allowing for even greater improvements in the chemical specificity. Here we describe our efforts to develop a suite of advanced mass spectral analysis and imaging techniques for the characterization and attribution of plastic explosives and other complex explosive mixtures from around the world. We will also provide initial feasibility studies for the characterization and differentiation of biological agents based on their unique molecular fingerprints. With the development of these very powerful “chemical signature microscopes” it is expected that significant advancements will be made in the field of forensics, both on the home front, and abroad.