With re-defined challenges in post-genome biology and medicine related to understanding the regulation and function of genes, proteins and multi-factorial disease, the development of accelerated and quantitative in-vivo observation of functional -omics at different system levels becomes a vital target. This proposal offers to develop therefore a next-generation biomedical imaging platform, designed to radically impact biomedical and drug discovery applications. The imaging strategy aims at resolving powerful optical reporters (fluorescent proteins, nanoparticles, optical probes) with 10-100 micron resolution and femptomole sensitivity through several millimeters to centimeters of tissue. This performance brings unprecedented ability to non-invasively visualize biological and molecular processes in-vivo in intact organisms over time.To achieve these goals, the proposal considers first the development of multi-spectral opto-acoustic tomography (MSOT) as a high performance method for revolutionizing biomedical imaging. Then, the proposal offers to develop powerful application areas in visualizing functional –omics, disease growth and drug effectiveness. The advancements offered herein can become a highly preferred biomedical imaging modality while offering ground-breaking imaging performance, safe non-ionizing radiation, an easy to disseminate platform, and unparalleled flexibility in capitalizing on powerful optical contrast using molecular reporters.