Eukaryotic cells are comprised of membrane-bound organelles, that must coordinate to maintain cellular homeostasis as well as to integrate environmental signals. This is of special importance for cell metabolism, since many cell types undergo metabolic reprogramming to sustain or adapt their function in response to altered nutrient levels, cell differentiation and activation. Immune cells, such as macrophages, strongly rely on metabolic switching to polarize to different effector states. Yet how organelles and organellar networks contribute to or even drive this process remains mostly unclear. To this end I aim to establish a systems-level spectral imaging approach, that will enable me to map the whole organellome in relation to a cell’s specific metabolic state. By doing so, I hope to gain novel insights into how organelles build a cellular architecture that shapes macrophage metabolism and immune function.