The molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target protein communities and the possibility of engineering extracellular signaling. At the IMSC 2024, I will describe the development and application of an optoproteomic technology termed LUX-MS that enables the targeted elucidation of acute protein interactions on and in between living cells using light-controlled singlet oxygen generators (SOGs). By using SOG-coupled antibodies, small molecule drugs, biologics, and intact viral particles, I will demonstrate the ability of LUX-MS to decode ligand-receptor interactions across organisms and to discover surfaceome receptor nanoscale organization with direct implications for drug action. LUX-MS-based decoding of surfaceome signaling architectures thereby provides a molecular framework for the rational development of theranostic strategies. In the context of the TumorProfiler project under development, I will further highlight new Swiss/ETH projects integrating proteotyping with other technologies for the digitization of patient samples, such as pharmacoscopy, which are geared towards supporting clinical decision-making.