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Existing models lack physiological relevance, particularly the vascular component critical for drug distribution and cardioprotection. To address this, we developed a heart\u2010on\u2010a\u2010chip (HoC) platform integrating human induced pluripotent stem cell (iPSC)\u2010derived cardiomyocytes, cardiac fibroblasts, and endothelial cells from a single cell line, ensuring genetic uniformity and native\u2010like cell\u2010cell interactions. The tri\u2010culture system maintained &gt;90% cell viability under perfusion for 7 days and exhibited functional maturity, as demonstrated by expected chronotropic responses to the \u03b2\u2010agonist isoproterenol. Crucially, the inclusion of endothelial cells mitigated doxorubicin\u2010induced cardiotoxicity, a protective effect absent in conventional models, highlighting the endothelial layer's role in replicating in vivo drug responses. 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