The blended-wing body is an aircraft configuration that has the potential to be more efficient than conventional large transport aircraft configurations with the same capability. However, the design of the blended-wing is challenging due to the tight coupling between aerodynamic performance, trim, and stability. Other design challenges include the nature and number of the design variables involved, and the transonic flow conditions. To address these issues, we perform a series of aerodynamic shape optimization studies using Reynolds-averaged Navier-Stokes computational fluid dynamics with a Spalart-Allmaras turbulence model. A gradient-based optimization algorithm is used in conjunction with a discrete adjoint method that computes the derivatives of the aerodynamic forces. A total of 273 design variables-twist, airfoil shape, sweep, chord, and span-are considered. The drag coefficient at the cruise condition is minimized subject to lift, trim, static margin, and center plane bending moment constraints. The studies investigate the impact of the various constraints and design variables on optimized blended-wing-body configurations. The lowest drag among the trimmed and stable configurations is obtained by enforcing a 1% static margin constraint, resulting in a nearly elliptical spanwise lift distribution. Trim and static stability are investigated at both on-and off-design flight conditions. The single-point designs are relatively robust to the flight conditions, but further robustness is achieved through a multi-point optimization.