Light‐sheet microscopy (LSM) enables us to strengthen the understanding of cardiac development, injury, and regeneration in mammalian models. This emerging technique decouples laser illumination and fluorescence detection to investigate cardiac micro‐structure and function with a high spatial resolution while minimizing photodamage and maximizing penetration depth. To unravel the potential of volumetric imaging in cardiac development and repair, we sought to integrate our in‐house LSM, Adipo‐Clear, and virtual reality (VR) with neonatal mouse hearts. We demonstrate the use of Adipo‐Clear to render mouse hearts transparent, the development of our in‐house LSM to capture the myocardial architecture within the intact heart, and the integration of VR to explore, measure, and assess regions of interests in an interactive manner. Collectively, we have established an innovative and holistic strategy for image acquisition and interpretation, providing an entry point to assess myocardial micro‐architecture throughout the entire mammalian heart for the understanding of cardiac morphogenesis.