A comprehensive approach to the detection of weapons of mass destruction containing special nuclear material (SNM) includes the ability to rapidly and efficiently determine a region of interest in three dimensions where atomic number, Z, is high and subsequently identify and quantify the nuclear isotopes in that region of space. Nuclear Resonance Fluorescence (NRF) combined with effective Z determination (EZ-3D™) provides for rapid scanning of seagoing containers, trucks and other vehicles in short times while providing high probabilities of detection for SNM and other contraband with low false alarms. Finding SNM with high probability of detection is associated with finding regions of high Z using EZ-3D™. Using NRF false positive events are eliminated in order to not restrict the flow of commerce. EZ-3D™ algorithms have been developed that use the non-resonant spectrum of backscattered photons and yield a signal with very high contrast between materials of moderately different Z. NRF provides a signal that is unique for most nuclei with Z>2. Different NRF signatures enable, for example, the discrimination between 235 U from 238 U. The NRF and EZ-3D™ techniques provide three dimensional displays of the contents of a voxel; respectively the isotopic concentrations and mass, and the effective Z.