Three dimensional (3D) tomography of biological specimens has always been challenging but it is essential to understand morphology, biology, and the associated interactions occurring in various tissues and systems. Over the last decade there has been an influx of focussed ion beam scanning electron microscopy (FIB-SEM) datasets, mostly generated with a Gallium FIB-SEM. The introduction of the Xenon plasma FIB-SEM allows for the investigation of larger samples (> 20 µm3) as it mills much faster than Gallium. Xenon is more chemically inert and less conductive than Galium resulting in the introduction of fewer artefacts. However, using a Xenon FIB-SEM comes with different challenges such as thicker sections being milled and more problems with drift and stability due to the larger beam size. Biological samples such as teeth, shells, and invertebrates are excellent candidates for this technique. Here we look at different invertebrate material investigated using the Galium FIB-SEM and the Xenon FIB-SEM to investigate these differences. In addition to 3D tomography, a variety of other techniques were also trialled in the Xenon FIB-SEM including TEM lamellae preparation, and cross-sectioning.