Stem cells are a promising solution for the treatment of heart failure due to their ability to repopulate injured myocardium and restore cardiac function. However, many hindrances (such as low survival/viability and integration of transplanted cells, poor homing and cardiac differentiation efficiency, and inadequate cell retention and engraftment) compromise the full regenerative potential provided by stem cells. Therefore, it is necessary to optimize stem cell/progenitor therapy to improve clinical efficacy. By analogy, in order for crops to grow, good seeds are needed. They also need sufficient fertilizer, herbicides, and pesticides to be "optimized." In this review, we provide a comprehensive overview of "seeds" (comparison of stem cell types, different combinations of stem cells, age, size, and dose of stem cells) and "fertilizers" (optimizing stem/progenitor cells and genetic strategies, preconditioning with drugs, and physical changes) for heart failure.