Cardiovascular diseases (CVDs) are the number one cause of death worldwide, taking 17.9 million lives each year. The rapid, sensitive, and accurate determination of cardiac biomarkers is vital for the timely diagnosis of CVDs. For accurate diagnosis, dependence on a single biomarker is unreliable because each one has also been linked to other diseases. To overcome this problem, the multiplexed determination of two or more markers has emerged as a promising alternative to single-marker analysis. Over the last 5 years, research interest in the development of biosensors for targeting multiple cardiac markers has increased. In this study, we critically reviewed the various multiplexed biosensing approaches reported during the last 5 years, categorizing them by signal readouts. Prospective detection configurations, capture probes, electrode design strategies, electrode types, nanomaterials, reporter tags, and assay types were reviewed, tabulated, and critically discussed. Then, their advantages and limitations were highlighted. For each category, we provided our perspective as well as the overall critical discussion. Lastly, we summarized potential commercial multiplexed cardiac biosensors and commented on the challenges and future prospects for such sensors.