Stem cell-based drug delivery for cancer therapy has steadily gained momentum in the past decade as several studies have reported stem cells' inherent tropism towards tumors. Since this science is still in its early stages and there are many factors that could significantly impact tumor tropism of stem cells, some contradictory results have been observed. This review starts by examining a number of proof-of-concept studies that demonstrate the potential application of stem cells in cancer therapy. Studies that illustrate stem cells' tumor tropism and discuss the technical difficulties that could impact the therapeutic outcome are also highlighted. The discussion also emphasizes stem cell imaging/tracking, as it plays a crucial role in performing reliable dose-response studies and evaluating the therapeutic outcome of treatment protocols. In each section, the pros and cons associated with each method are highlighted, limitations are underlined, and potential solutions are discussed. The overall intention is to familiarize the reader with important practical issues related to stem cell cancer tropism and in vivo tracking, underline the shortcomings, and emphasize critical factors that need to be considered for effective translation of this science into the clinic.