This paper studies the problem of scheduling flexible job shops with setup times where the setups are sequence-dependent. The objective is to find the schedule with minimum total tardiness. First, the paper develops a mathematical model in the form of mixed integer linear programming and compares it with the available model in the literature. The proposed model outperforms the available model in terms of both size complexity and computational complexity. Then, an effective metaheuristic algorithm based on iterated local search is proposed and compared with a tabu search and variable neighbourhood search algorithms proposed previously for the same problem. A complete experiment is conducted to evaluate the algorithms for performance. All the results show the superiority of the proposed algorithm against the available ones.