In the past 5 years, the life sciences community has witnessed the progression of the genomics and proteomics world into the spatial domain. This was in large part due to a strong desire to not only know which genes were being turned on and which proteins were being expressed, but also precisely where in a much larger context. This contextual data is leading to discoveries about not just how the biology is acting but rather where it is acting, leading to the terminology of “actionable biology.” This concept of actionable biology is leading to a much deeper understanding of diseases and genetic disorders and is transforming the developments of treatments, cures, and drug discoveries. Certainly, the spatial concept easily lends itself to microscopy methods, and we have seen the release of many powerful instruments on the market dedicated to spatial omics applications. Initially, this work was almost exclusively being done on thin tissue sections or monolayers of cells, and therefore, 2D imaging using widefield microscopy was sufficient. However, biology is inherently 3D, and the desire to resolve information in the z-dimension, even in relatively thin sections, is increasing. Furthermore, we see researchers pushing these methods into even thicker tissue samples, and therefore, this obviates the need for an optical sectioning microscopy method to accomplish the imaging goals. In addition to being able to optically section thick samples, the ideal system should also possess spectral flexibility to meet the demands of the growing number of biomarkers needed to be interrogated in a single imaging cycle, as well as RNAScope and smFISH probes pushing out into the NIR wavelength range. The LSM 980 with NIR detection provides the most flexible spectral acquisition of any confocal on the market. With new tools such as LSM Plus to further increase resolution and sensitivity, we can now acquire the signature of even up to 10 or more markers in a single scan; therefore, increasing throughput and productivity.