This paper presents a multi-disciplinary design optimization (MDO) framework for design of a general aviation aircraft wing considering the effects of tractor propellers on the wing aerodynamic characteristics. In pursuit of this objective, a wing–propeller full-interaction aerodynamic routine was developed and integrated with structural and performance models. A substantive contribution of the work is the approach for effectively modeling wing effects on propeller slipstream development while still leveraging traditional propeller and wing analysis tools. Several optimizations were carried out, starting from an existing aircraft design, to test different local and global surrogate-based optimization frameworks and to allow for the assessment of the resulting solutions and corresponding computational performance metrics. Examination of the total function calls and run times showed that the use of surrogate models improves overall optimization performance, provided that suitable surrogate modeling techniques are chosen.