Cardiovascular diseases (CVDs) are the leading cause of rising morbidity and mortality among humans worldwide; however, our approach to the pathogenesis, exploration, and management of CVDs still remains limited. As the heart consists of cardiomyocytes, cardiac fibroblasts, endothelial cells, smooth muscle cells, and several types of cells, different types of dysfunction in the interplay between organelles play an important damaging role, resulting in cardiac pathologies. The interplay between cellular organelles is intricate and vital for maintaining cellular homeostasis, as highlighted by multiple diseases linked to the dysfunction of both organelles. Many studies have revealed the potential mechanisms by which organelles communicate with each other and regulate the pathological processes of CVDs together. However, gaps remain in fully understanding the complexity of these interactions and translating these insights into therapeutic approaches. In this review, we summarized how the interplay between cellular organelles in the cardiomyocytes alters in various heart diseases. We find underexplored areas, such as the crucial signaling pathways governing organelle communication, and discuss their implications for disease future progression. Furthermore, we evaluate emerging potential medicines aimed at restoring organelle interactions. Finally, we propose future directions for researching to advance the development of novel medicines and therapies, addressing current gaps and providing a theoretical basis for improved clinical outcomes in CVDs.