Despite primary percutaneous coronary intervention (PPCI) and the availability of optimal medications, including dual antiplatelet therapy (DAPT), most patients still experience major adverse cardiovascular events (MACEs) due to frequent recurrence of thrombotic complications and myocardial infarction (MI). MI occurs secondary to a massive loss of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and cardiomyocytes (CMs). The adult cardiovascular system gradually loses the ability to spontaneously and regularly regenerate ECs, VSMCs, and CMs. However, human cells can be induced by cytokines and growth factors to regenerate human-induced pluripotent stem cells (hiPSCs), which progress to produce cardiac trilineage cells (CTCs) such as ECs, VSMCs, and CMs, replacing lost cells and inducing myocardial repair. Nevertheless, the processes and pathways involved in hiPSC-CTC generation and their potential therapeutic effects remain unknown. Herein, we provide evidence of in vitro CTC generation, the pathways involved, in vivo transplantation, and its therapeutic effect, which may provide novel targets in regenerative medicine for the treatment of cardiovascular diseases (CVDs).