Although intratumoral chemotherapy administration has been evaluated in the past, its results have not been frequently comparable to those from systemic administration. We recently described microdialysis as a method for local chemotherapy administration with increasing effectiveness while reducing systemic toxicity. We present a mathematical model which supports the successful application of this procedure in optimizing the administered drug in different cases, using informatics tools and considering several parameters. We also review and discuss important aspects of cancer biology that should be taken into consideration in cancer chemotherapy, such as tumor heterogeneity, drug resistance and metastasis, and how this technique may be used to overcome any set-backs presented by these.