With the advent of complement therapeutics, it becomes critical to understand whether and how complement contributes to the pathophysiology of diseases affecting the kidney to provide personalized treatments. During the talk, we will illustrate how we developed an ultra-high in situ Complementomics approach using the COMET™ Imager. We combined the staining for complement proteins, receptors and activation fragments with tissue structure markers and markers for phenotyping of the immune infiltrate. Through this innovative approach, we successfully untangled the intricacies of complement activation within diverse kidney diseases and kidney cancers, as well as its interconnectedness with the infiltration of immune cells. Ultimately, this method sheds light on the role of complement in various disorders, opening doors to the discovery of novel biomarkers and therapeutic strategies.