Nowadays, there is a significant and growing interest in improving the efficiency of vehicle design processes through the development of tools and techniques in the field of MDO. Specifically, in aerostructure design, aerodynamic and structural variables influence each other and have a joint effect on quantities of interest like weight or fuel consumption and, as such, MDO arises as a powerful tool for automatically making interdisciplinary trade-offs. In the aircraft design context, the process generally involves mixed continuous and categorical design variables. For instance, the size of an aircraft’s structural parts can be described using continuous variables, while discrete variables may include either integer variables, like the number of panels, or categorical variables, like cross-sections or material choices. The objective of this Philosophiae Doctor (Ph.D) thesis is to propose an efficient approach for optimizing a multidisciplinary black-box model when the optimization problem is constrained and involves a large number of mixed integer design variables (typically 100 variables). The targeted optimization approach, called EGO, is based on a sequential enrichment of an adaptive surrogate model and, in this context, GP surrogate models are one of the most widely used in engineering problems to approximate time-consuming high fidelity models. EGO is a heuristic BO method that performs well in terms of solution quality. However, like any other global optimization method, EGO suffers from the curse of dimensionality, meaning that its performance is satisfactory on lower dimensional problems, but deteriorates as the dimensionality of the optimization search space increases. For realistic aircraft design problems, the typical size of the design variables can even exceed 100 and, thus, trying to solve directly the problems using EGO is ruled out. The latter is especially true when the problems involve both continuous and categorical variables increasing even more the size of the search space. In this Ph.D thesis, effective parameterization tools are investigated, including techniques like partial least squares regression, to significantly reduce the number of design variables. Additionally, Bayesian optimization is adapted to handle discrete variables and high-dimensional spaces in order to reduce the number of evaluations when optimizing innovative aircraft concepts such as the “DRAGON” hybrid airplane to reduce their climate impact.