Recent breakthroughs in optical microscopy have enabled in vivo imaging of the embryonic heart as it develops and gains function. Despite these advances, it remains difficult to simultaneously characterize heart morphology, heart function (the embryonic heart is beating before it is fully developed), and gene expression levels. We have developed computational tools to capture, process, and combine images acquired with different microscopy modalities, at different temporal and spatial scales, and over multiple samples, in an effort to build a multi-dimensional model of the beating and developing heart where morphology, function, and genetics can be simultaneously studied. Here, I will discuss image acquisition protocols and reconstruction strategies to overcome instrumentation and biological limitations that prevent simultaneous acquisition of these large, high-dimensional data sets. These tools will facilitate quantitative and systematic characterization of both morphology and function and study their relationship to genetic and epi-genetic factors that affect development in normal and diseased hearts.