The malignant tumor is the main cause of human deaths worldwide. Current therapies focusing on the tumor itself have achieved unprecedented benefits. Various pro-tumorigenic factors in the tumor microenvironment (TME) could abolish the effect of cancer therapy. Mesenchymal stromal cells (MSCs) are one of the substantial components in the tumor microenvironment, contributing to tumor progression. However, MSCs are not inherently tumor-promoting. Indeed, they acquire pro-tumorigenic properties under the education of the TME. We herein review how various elements in the TME including tumor cells, immune cells, pro-inflammatory factors, hypoxia, and extracellular matrix influence the biological characteristics of MSCs through complex interactions and demonstrate the underlying mechanisms. We also highlight the importance of tumor-associated mesenchymal stromal cells (TA-MSCs) in promoting tumor progression. Our review gives a new insight into the TA-MSCs as a potential tumor therapeutic target. It is anticipated that subverting MSCs education will facilitate the outbreak of therapeutic strategies against tumors.