Micromachined mechanical variable capacitor is a key component of many microelectromechanical systems (MEMS) devices, such as pressure sensor, accelerometer, gyroscope, electrometer, etc. Optimization of these devices require a systematic consideration of parameter design in both mechanical and electrical domains. This chapter introduces the system-level modelling of a variable capacitor-based MEMS electrometry system. To simultaneously simulate the mechanical and electrical components, Matlab Simulink was adopted as the simulation environment to build the system model. Four main modelling blocks were developed to model the entire system, including electrostatic force generator, equivalent circuit representation of spring-mass-damper mechanical system, time-dependent variable capacitor controlled by in-line equation, and integration of variable capacitor into the actual detection circuitry. The whole electrometry system was successfully simulated in Simulink, and the detailed simulation results are shown in this chapter, such as the waveforms of driving force, shuttle displacement, time-varying capacitance and charge induced output voltage. The simulated results agreed well with the experimental results, for example, the simulated charge sensitivity is 7.2×107 V/C, which is close to the experimental results of 9.5×107 V/C with the same design parameters. Using this technique, any variable capacitor-based MEMS sensors can be modelled in Simulink by simply changing the mathematical calculation blocks to implement the in-line equation for the time-dependent capacitance. Therefore, this technique provides a useful tool that allows a fully combined simulation of both mechanical and electronic systems.