Aircraft design optimization and airline allocation problems are two separate and wellresearched disciplines, but very little literature exists that solved the design and allocation problems simultaneously. Among the limited number of related efforts that combine them, most follow a sequential decomposition strategy. This sequential strategy has been successful in addressing the combined large-scale problem but the approach does not capture the coupling that exists between the aircraft design and airline allocation disciplines. Solving the aircraft design and airline allocation as a monolithic problem makes it a Mixed Integer Non-Linear Programming problem which is very difficult to solve for large numbers of integer variables. Because no existing generalized MINLP solver can address this problem, this work proposes a new algorithm combining branch and bound, Efficient Global Optimization, Kriging Partial Least Squares, and gradient-based optimization to solve MINLP problems with 100's of integer design variables, 1000's of continuous design variables. The algorithm was applied to an 8 route coupled aircraft design and allocation problem with the 19 allocation variables and solving a 6000 variable aircraft design optimization problem using an Euler CFD simulation. This test problem provides several key challenges for a MINLP problem: a moderate integer design space, a large continuous design space, and expensive analysis models.