A method for optimizing the inner shape of brass instruments using sound simulations is presented. This study considers different objective functions and constraints (representative of both the intonation and the spectrum of the instrument) for a relatively large number of design variables. A complete physics-based model, taking into account the instrument and the musician's embouchure, is used to simulate steady regimes of sounds by means of the harmonic balance technique, the instrument being represented by its input impedance. The design optimization variables are related to the geometrical dimensions of the resonator. The embouchure's parameters are varied during the optimization procedure to obtain an average behavior of the instrument. The objective and constraint functions of the optimization problem are evaluated using the physics-based simulation model, which is computationally expensive. Moreover, the gradients of the objective and constraint functions can be discontinuous, unavailable, or hard to approximate reliably. Therefore, a surrogate-assisted derivative-free optimization strategy using the mesh adaptive direct search algorithm was employed. One example of a B♭ trumpet's bore is used to demonstrate the effectiveness of the design optimization approach: the obtained results improve previously reported objective function values significantly.