SWOPT is a novel imaging technology that will break through the penetration limits of optical microscopy to visualize individual cells and their function in vivo through several millimeters to centimeters of depth. SWOPT will exploit (1) optoacoustic imaging (OAI), a modality which combines signal generation similar to optical imaging with the whole-animal imaging capability of ultrasound readout, and uniquely augment it with (2) photoswitching to resolve signals from single labeled cells from deep within live tissue. This will achieve volume sampling abilities surpassing any optical microscopy by at least three orders of magnitude (> 5 x 5 x 5 mm imaging volume). SWOPT will develop the necessary breakthrough instrumentation and concepts: unique multiplexed diode illumination, novel ultra-wideband transducer technology, dedicated inversion algorithms that incorporate photoswitching in the three-dimensional reconstructions, and uniquely tailored classes of photo-switching transgene and synthetic molecular tools. The exceptional capabilities of SWOPT will be demonstrated by proof-of-concept work resolving cellular dynamics and functions in a whole tumor in a model of renal cancer in vivo. SWOPT builds on the world-leading expertise in the disciplines of OA imaging technology (Ntziachristos GER), applied mathematics (Unser CH), and cancer metabolism (Frezza UK) and is driven by excellent young researchers in protein-engineering (Stiel GER) and chemical synthesis (Szymanski NL) and supported by the science-to-technology focus of ambitious high-tech SMEs (Sonaxis FRA, iThera GER, Spear GER). SWOPT’s uniquely comprehensive, yet detailed imaging will enable examination of whole tissues in vivo with the same ease, flexibility and, eventually, abundance of tools paralleling fluorescence microscopy, thus bringing research and understanding of living organisms to the next level. As an affordable imaging technology, SWOPT aspires to become routine in life science and bio-medical research.