The coupled fluid-solid simulations have been developed to analyze the density measurement sensitivity (DMS) of resonant micro-cantilevers with different shapes, dimensions and operation modes. The analytical formulas have been established to illustrate the relationship of resonant frequency shifts and densities of working fluids. The coupled fluid-solid simulation analyses and experimental results have been used to study the effects of micro-cantilevers with different dimensions on the DMS under bending and torsion modes. The influences of micro-cantilevers with different shapes on the DMS have been also discussed and analyzed. It is concluded that the length and free end width of micro-cantilever as well as operation mode are the key factors affecting the DMS. In addition, the proposed coupled fluid-solid simulation method is an important instruction in the aspect of micro-cantilever design. At the last, the resonant frequency stability and resolution of sensor were analyzed to better understand the sensor’s performance.