In recent years there has been interest in research related to hyperthermia combined with radiation and cytotoxic drugs to enhance the killing of tumors. When heating the tumor tissue, the crucial problem is keeping the temperature of the normal tissue surrounding the tumor below a certain threshold so as not to cause damage to the tissue. Hence, in order to control the process, it is important to obtain a temperature field of the entire treatment region. Recently, we have developed a numerical method for obtaining an optimal temperature distribution in a triple-layered skin structure. In this article, we extend our study to a triple-layered skin structure embedded with multilevel blood vessels, and develop a numerical method for obtaining an optimal temperature distribution. © 2006 American Institute of Physics.