Heart failure is a syndrome that results from varying types of cardiomyopathies and is a major cause of death worldwide. Often, the molecular mechanism underlying cardiomyopathy is unknown, and researchers were mostly limited to non-invasive techniques in patients and animal models, but the advances in tissue engineering and in vitro disease modeling have opened new avenues to bridge the gaps left by traditional methods. New models have increased our understanding of cardiac physiology and pathology. The use of pluripotent stem cells and robust protocols of cardiac differentiation combined with state-of-the-art gene-editing techniques have allowed for significant improvements of human in vitro models. Technological advances have enabled better phenotyping of small animal models. As such, it is now accepted that the heart is more than a mechanical organ and can affect other organs in a myriad of ways and this requires new translational methods to appropriately study heart diseases. The methods collection will highlight novel techniques at various levels of translation research related to cardiomyopathies and heart failure, including tissue engineering, specific analyses in animal models, and novel analyses in patients.