Mesenchymal stem cells (MSCs) are specialized cells that can differentiate into various types of cells. MSCs can be utilized to treat cancer. However, a MSC is considered a double-edged sword, because it can promote tumor progression and support cancer cell growth. Likewise, MSC-derived exosomes (MSC-Exos) carry various intracellular materials and transfer them to other cells. MSC-Exos could also cause tumor progression, including brain cancer, breast cancer, hepatic cancer, lung cancer, and colorectal cancer, and develop resistance against therapies, mainly chemotherapy, radiotherapy, and immunotherapy. An MSC-Exo promotes tumor development and causes drug resistance in various cancer types. The mechanisms involved in cancer drug resistance vary depending on the cancer cell heterogeneity and complexity. In this article, we have explained the various biomarkers and mechanisms involved in the tumor and resistance development through MSC-Exos in different cancer types.