Softness of nanomedicines plays a significant role in antitumor drug delivery and efficiency. Examining and finding optimized contact models to verify and choosing best nanomedicine mechanical properties for each cancer genotype has a profound effect in nano based drug delivery. In this research, appropriate contact models have been identified and used for determining the modulus of elasticity of SW48 cancer cells based on the Atomic Force Microscope. The Sobol method was chosen for the sensitivity analysis of Hertz, Lundberg, Dawson, Nikpour, and Hoeprich models. By comparing the sensitivity percentages of various parameters, it was realized that different theories can be used to identify different properties of cancer cells. Considering the results of the sensitivity percentage of various parameters, the Lundberg and Hertz theories can be employed to identify the modulus of elasticity. The Hoeprich contact model can be used to determine the Poisson’s ratio. Ultimately, by using the results obtained from analysis, the modulus of elasticity of cancer cell SW48 was computed experimentally based on the theories of Lundberg and Hertz. Results and method can be directly use in identifying mechanical properties of cancer cells and obtain nanomedicine softness range for best efficiency of nano based drug delivery.