Cancer chemotherapies often have poor selectivity, thus causing severe side effects due to undesired systemic exposure. Targeting of drug action is an important goal as it reduces non-desired side effects, allowing the use of higher doses that can potentially provide more effective cure. Present research largely focuses on allocating highly specific molecules as targets of cancer therapy. However, the enormous heterogeneity and dynamic nature of tumors makes it extremely challenging to identify universal target molecules. In the novel approach proposed here we hypothesize that mechanical based interactions between drug carriers and cells can largely promote drug targeting and selectivity. In many cancers, it is well-established that the flexibility and deformability of the cells are correlated with their metastatic potential. We therefore hypothesize that cancer cells, but not normal cells, would be able to engulf and uptake particles whose internalization requires massive shape change. This notion motivated our vision of a “Mechanical targeting” (MT) method, in which intrinsic deformability of cells will control the specificity of drug carrier uptake. The rationale of the proposed study is that by considering physical parameters of cells, the mechanical properties of drug delivery systems (DDS) can be tuned to achieve selective uptake. We thus propose to develop tools for the rational design of DDS for personalized nanomedicine that will apply simple tests performed on a patient’s own cells for optimized treatments.