Over the last decade, advancements in stem cell biology have yielded a variety of sources for stem cell-based cardiovascular investigation. Stem cell behavior, whether to maintain its stable state of pluripotency or to prime toward the cardiovascular lineage is governed by a set of coordinated interactions between epigenetic, transcriptional, and translational mechanisms. The science of incorporating genes (genomics), RNA (transcriptomics), proteins (proteomics), and metabolites (metabolomics) data in a specific biological sample is known as systems biology. Integrating systems biology in progression with stem cell biologics can contribute to our knowledge of mechanisms that underlie pluripotency maintenance and guarantee fidelity of cardiac lineage specification. This review provides a brief summarization of OMICS-based strategies including transcriptomics, proteomics, and metabolomics used to understand stem cell fate and to outline molecular processes involved in heart development. Additionally, current efforts in cardioregeneration based on the "one-size-fits-all" principle limit the potential of individualized therapy in regenerative medicine. Here, we summarize recent studies that introduced systems biology into cardiovascular clinical outcomes analysis, allowing for predictive assessment for disease recurrence and patient-specific therapeutic response.