In the present paper, for the first time, Invasive Weed Optimization (IWO) algorithm was utilized to optimize the reloading pattern of a nuclear reactor. This algorithm has been inspired by flexible, resistant and invasive behavior of weed in search for resources and appropriate location for growth and reproduction in the environment. The purpose of the optimization performed in this research was to achieve a reloading pattern with maximum effective multiplication factor along with safe maximum power peaking factor. Given that the diversity of loadable fuel assemblies was higher in the second cycle, as compared to other operational cycles, the optimization computations were conducted in this cycle to ensure high performance of the designed process under the most complicated conditions. In this respect, in order to assess fuel composition of the remaining assemblies from the first cycle and accurately calculate the objective parameters of the arrangements considered in the course of the optimization process, a program was developed wherein WIMSD5-B and CITATIO-LDI2 codes were utilized for neutronic simulations and WERL code was adopted for thermo-hydraulic modeling of the reactor core. Once finished with the optimization process, in an attempt to assure safety and optimality of the proposed arrangement during the operational cycle, the developed computational program was adopted to simulate time-dependent thermo-neutronic behavior of the reactor core during the second operational cycle. In addition, in order to ensure optimality of the proposed arrangement, firstly, it was compared to the arrangement proposed by the Russian contractor for a similar VVER-1000 reactor (Balakovo Nuclear Power Plant), and then, in another investigation, a comparison was made between the results of optimization using IWO algorithm and those using Genetic Algorithm (GA) and Imperialist Competitive Algorithm (ICA). Results of all of the comparisons performed herein were indicative of superiority of the proposed optimization process in this research in terms of speed and comprehensiveness of the search process, and, more importantly, desirability of the proposed pattern.