Micro fabricated cantilever beam smart immunosensor was modeled using "Intellisuite" software to detect nanogram level antigen. The FEM simulations were carried out with immunoglobulin antibody, IgG for the detection of C -reactive protein. The effect of geometry of the cantilever beam with different number of holes and thickness of Si piezo resistive-patch on the sensor performance and signal transduction was studied. The effect of nature of Si and CNT piezo resistive-patch on the sensor performance was also investigated. Considering the response of stress and sensitivity, CNT piezo resistive patch is more suitable for the development of smart sensor. A cantilever beam immunosensor 100 μm long, 50 μm wide and 2.4 μm thick with one hole 3 μm long and 6 μm wide in the beam and CNT piezo-patch 100 nm thick is a more promising system for the fabrication for the detection of C -reactive protein. The modeled sensor can detect CRP even at a low concentration of 11.0 ng/ml.