Despite considerable improvement in diagnostic modalities and therapeutic options over the last few decades, the global burden of ischemic heart disease is steadily rising, remaining a major cause of death worldwide. Thus, new strategies are needed to lessen cardiovascular events. Researchers in different areas such as biotechnology and tissue engineering have developed novel therapeutic strategies such as stem cells, nanotechnology, and robotic surgery, among others (3D printing and drugs). In addition, advances in bioengineering have led to the emergence of new diagnostic and prognostic techniques, such as quantitative flow ratio (QFR), and biomarkers for atherosclerosis. In this review, we explore novel diagnostic invasive and noninvasive modalities that allow a more detailed characterization of coronary disease. We delve into new technological revascularization procedures and pharmacological agents that target several residual cardiovascular risks, including inflammatory, thrombotic, and metabolic pathways.