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Both tyrosine kinase inhibitors (tki) and mammalian target of rapamycin (mTOR) inhibitors are oral targeted therapies that are used for the treatment of a variety of malignancies. Due to the growing evidence for drug exposure-response relationships, in combination with their high interpatient variability in pharmacokinetics (pk) and a fixed dosing regimen, it is hypothesized that dose individualization of oral targeted therapies may lead to better treatment outcomes both in terms of efficacy as well as toxicity. This thesis describes the results of different studies that investigated dose optimization strategies of oral targeted therapies used in oncology, with a focus on the TKIs pazopanib and sunitinib and the mTOR inhibitor everolimus.