Mesenchymal stem/stromal cells (MSCs) are critical for blood cell development and are valuable resources for regenerative medicine. However, MSCs can promote the progression and aggressiveness of blood cancers like leukemia through both contact-dependent and contact-independent communication. Contact-dependent communication is mediated by temporary intercellular tubes called tunneling nanotubes (TNTs) and by gap junctions, shorter channels that span adjacent cell membranes. The molecules and organelles that pass through these openings can promote cancer cell survival and drug resistance. In contact-independent communication, MSCs release proteins that interact with receptors on nearby cancer cells or microvesicles (MVs) that transport genetic materials or other biological molecules, triggering signaling pathways related to immunosuppression and cancer progression. Notably, the communication can occur in both directions, contributing to an intercellular dialogue that shapes the tumor microenvironment. Deeper research into the different types of “conversations” between MSCs and various blood cancers might help researchers treat these diseases more effectively and better understand the dual roles of MSCs as both beneficial stem cells and cancer promoters.