During radiation therapy, it is necessary to monitor the irradiated position and energy deposited in the patient. In general, calculations before photon exposure or 2D measurement of transmitted photons have been widely used for dose estimation. In this research, we propose real-time 3D dose measurement using Compton imaging technology. On the basis of the Monte-Carlo method, we designed a multiple scattering Compton camera system (MSCC) with semiconductor and scintillation detectors. The MSCC was constructed with two semiconductor detectors as scatter detectors and a CWO scintillator detector as an absorber detector. The two planar semiconductor arrays consisted of 40 × 40 pixels, each with a size of 1 × 1× thickness mm3, and the other CWO array consisted of 40 × 40 pixels, each with a size of 1 × 1 × thickness mm3. The design parameters such as the types of semiconductors, detector thicknesses and distances between detectors were optimized on the basis of the detection efficiency and angular resolution of reconstructed images for a point source. Under the optimized conditions, uncertainty factors in geometry and energy were estimated for various the inter-detector distances. We used a source corresponding to photons scattered from a water phantom exposed to the 6-MeV peak X-ray. According to our simulation results, the figure of merit (FOM) reached its maximum value when the inter-detector distance is 3 cm. In order to achieve a high FOM, we chose 1 cm as the optimum thickness for scattering detectors. The position uncertainty caused by the pixelization effect was the major factor to degrade the angular resolution of the reconstructed images and the degradation caused by energy broadening was less than expected. The angular uncertainties caused by Doppler broadening and incorrect sequencing were minimal compared with that of pixelization. Our simulation showed the feasibility of using the semiconductor based Compton camera to monitor the exposed dose in 3D radiation therapy.