GATE is a software dedicated to Monte Carlo simulations in Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). An important disadvantage of those simulations is the fundamental burden of computation time. This manuscript describes three different techniques in order to improve the efficiency of those simulations. Firstly, the implementation of variance reduction techniques (VRTs), more specifically the incorporation of geometrical importance sampling, is discussed. After this, the newly designed cluster version of the GATE software is described. The experiments have shown that GATE simulations scale very well on a cluster of homogeneous computers. Finally, an elaboration on the deployment of GATE on the EGEE (Enabling Grids for E-Science in Europe) Grid will conclude the description of efficiency enhancement efforts. The three aforementioned methods improve the efficiency of GATE to a large extent and make realistic patient-specific overnight Monte Carlo simulations achievable.