Acquisition of three-dimensional (3D) spectral data is nowadays common using many different microanalytical techniques. In order to proceed to the 3D reconstruction, data processing is necessary not only to deal with noisy acquisitions but also to segment the data in term of chemical composition. In this article, we demonstrate the value of multivariate statistical analysis (MSA) methods for this purpose, allowing fast and reliable results. Using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) coupled with a focused ion beam (FIB), a stack of spectrum images have been acquired on a sample produced by laser welding of a nickel–titanium wire and a stainless steel wire presenting a complex microstructure. These data have been analyzed using principal component analysis (PCA) and factor rotations. PCA allows to significantly improve the overall quality of the data, but produces abstract components. Here it is shown that rotated components can be used without prior knowledge of the sample to help the interpretation of the data, obtaining quickly qualitative mappings representative of elements or compounds found in the material. Such abundance maps can then be used to plot scatter diagrams and interactively identify the different domains in presence by defining clusters of voxels having similar compositions. Identified voxels are advantageously overlaid on secondary electron (SE) images with higher resolution in order to refine the segmentation. The 3D reconstruction can then be performed using available commercial softwares on the basis of the provided segmentation. To asses the quality of the segmentation, the results have been compared to an EDX quantification performed on the same data.