Iron is an essential inorganic element for various cellular events. It is directly associated with cell proliferation and growth; therefore, it is expected that iron metabolism is altered in tumor cells which usually have rapid growth rates. The studies on iron metabolism of tumor cells have shown that tumor cells necessitated higher concentrations of iron and the genes of iron uptake proteins were highly over-expressed. However, there are limited number of studies on overall iron metabolism in drug-resistant tumor cells. In this article, we evaluated the studies reporting the relationship between drug resistance and iron metabolism and the utilization of this knowledge for the reversal of drug resistance. Also, the studies on iron-related cell death mechanism, ferroptosis, and its relation to drug resistance were reviewed. We focus on the importance of iron metabolism in drug-resistant cancer cells and how alterations in iron metabolism participate in drug-resistant phenotype.