Although model updating has been widely applied using a specific optimization algorithm with a single objective function using frequencies, mode shapes or frequency response functions, there are few studies that investigate hybrid optimization algorithms for real structures. Many of them did not take into account the sensitivity of the updating parameters to the model outputs. Therefore, in this paper, optimization algorithms and sensitivity analysis are applied for model updating of a real cable-stayed bridge, i.e., the Kien bridge in Vietnam, based on experimental data. First, a global sensitivity analysis using Morris method is employed to find out the most sensitive parameters among twenty surveyed parameters based on the outputs of a Finite Element (FE) model. Then, an objective function related to the differences between frequencies, and mode shapes by means of MAC, COMAC and eCOMAC indices, is introduced. Three metaheuristic algorithms, namely Gravitational Search Algorithm (GSA), Particle Swarm Optimization algorithm (PSO) and hybrid PSOGSA algorithm, are applied to minimize the difference between simulation and experimental results. A laboratory pipe and Kien bridge are used to validate the proposed approach. Efficiency and reliability of the proposed algorithms are investigated by comparing their convergence rate, computational time, errors in frequencies and mode shapes with experimental data. From the results, PSO and PSOGSA show good performance and are suitable for complex and time-consuming analysis such as model updating of a real cable-stayed bridge. Meanwhile, GSA shows a slow convergence for the same number of population and iterations as PSO and PSOGSA.