The purpose of this paper is to present a hybrid meta-heuristic based on genetic algorithms, simulated annealing, variable neighborhood descent and path relinking for solving the variant of the unrelated parallel machine scheduling problem considering sequence-dependent setup times. The authors carried out computational experiments on literature problem instances proposed by Vallada and Ruiz (2011) and Arnaout et al. (2010) in order to test the performance of the proposed meta-heuristic. The objective function adopted was makespan minimization, and we used relative deviation, average and population standard deviation as performance criteria. The results indicate the competitivity of the proposed approach and its superiority in comparison with several other algorithms. On small instances proposed by Vallada and Ruiz (2011) and on small and large instances proposed by Arnaout et al (2010), the proposed approach presented the best results in most tested problem instances. On small instances proposed by Vallada and Ruiz (2011), as well as on small and large instances proposed by Arnaout et al (2010), the proposed approach presented the best results in most tested problem instances. The proposed approach presented high-quality results, with an innovative hybridization of a genetic algorithm and neighborhood search algorithms, tested in diverse instances of literature. Furthermore, the case study demonstrated that the proposed approach is recommended for solving real-world problems.