Three-dimensional materials science (3DMS) has become a burgeoning field providing unique and novel insights to a myriad of materials issues ranging from kinetics of solidification, evaluation of complex microstructures, in-situ observation of response, and even post-mortem failure analysis. While largely exploratory in the early 2000s, two decades of development have provided much in advancing experimental hardware, software packages and overall computational power. These developments have reduced both the barrier to entry and many previous limitations. Using a RoboMET.3DTM, Sandia National Laboratories has advanced much of its 3DMS investigations from fundamental research to pressing concerns in engineered components. To illustrate, examples of new insights, failure mode discoveries and lot-to-lot variations in singular material systems and engineered multi-material assemblies, as obtained via three-dimensional reconstruction, will be provided. Additionally, a few observations regarding error estimation and the impact of image segmentation decisions on final results will also be highlighted.