Cardiovascular disease is the leading cause of death worldwide necessitating accurate human disease models to improve our understanding and facilitate preclinical trials. Cardiac organoid models can recapitulate the 3D microenvironment and integrate the different cell types found in native hearts. This project aims to deliver an advanced pre-clinical human model for modelling heart disease. Induced pluripotent stem cells (iPSCs) were differentiated into cardiomyocytes, endothelial cells, and sympathetic neurons and then combined to form vascularised and innervated cardiac organoids which were maintained for up to 4 weeks. Cardiac organoids exhibited spontaneous and synchronous contractions (168±7 bpm) at 1-week. Histology showed CD31+ endothelial networks and tyrosine hydroxylase+ neural networks interspersed throughout the organoid. Single-cell RNAseq confirmed organoid reproducibility and identified input cell types. Organoids significantly increased lactate dehydrogenase release in response to doxorubicin-induced cardiotoxicity (P<0.05) and simulated ischaemia-reperfusion injury (P<0.05) indicating the capability of the organoids to simulate standard cardiac responses to injuries. In conclusion, human iPSC-derived cardiomyocytes, endothelial cells and sympathetic neurons self-assembled within our proprietary organoid model to generate beating cardiac tissue with a microvascular and neural network. This in vitro human cardiac tissue will be an ideal pre-clinical human model to study and develop novel therapeutics for heart diseases.