Cardiac regeneration aims to reconstruct the heart contractile mass, preventing the organ from a progressive functional deterioration, by delivering pro-regenerative cells, drugs, or growth factors to the site of injury. In recent years, scientific research focused the attention on tissue engineering for the regeneration of cardiac infarct tissue, and biomaterials able to anatomically and physiologically adapt to the heart muscle have been proposed as valuable tools for this purpose, providing the cells with the stimuli necessary to initiate a complete regenerative process. An ideal biomaterial for cardiac tissue regeneration should have a positive influence on the biomechanical, biochemical, and biological properties of tissues and cells; perfectly reflect the morphology and functionality of the native myocardium; and be mechanically stable, with a suitable thickness. Among others, engineered hydrogels, three-dimensional polymeric systems made from synthetic and natural biomaterials, have attracted much interest for cardiac post-infarction therapy. In addition, biocompatible nanosystems, and polymeric nanoparticles in particular, have been explored in preclinical studies as drug delivery and tissue engineering platforms for the treatment of cardiovascular diseases. This review focused on the most employed natural and synthetic biomaterials in cardiac regeneration, paying particular attention to the contribution of Italian research groups in this field, the fabrication techniques, and the current status of the clinical trials.