Over the past several years, efforts have been made to establish in-vitro environments of human-like organs that imitate human physiology. The human heart is an important organ to emulate, due to the prevalence of cardiac disease and the high incidence of drug-induced cardiac toxicity. Here, we present a heart-on-chip platform capable of maintaining human tissue for over a month in vitro under physiological conditions. Mitochondrial respiration was monitored in real time using two-frequency phase modulation of tissue-embedded phosphorescent microprobes. Metabolic fluxes were measured by the microfluidic on-chip electrochemical sensor unit, measuring glucose, glutamine, glutamate, and lactate, providing real-time analysis of minute shifts in key metabolic fluxes. Electrophysiological activity was simultaneously measured by extracellular field potentials, recorded using an on-chip nano-fabricated multi-electrode array (MEA) system. We combine the data to provide elaborate real-time assessment of the organoid`s activity and health, allowing us to investigate the response for the prediction of drug-induced cardiotoxicity and perfusion injuries. Our microfluidic platform reveals the dynamics and strategies of cellular adaptation to cardiac damage, a unique advantage of organ-on-chip technology.