The technology of missiles and of their countermeasures is evolving continuously. High-power lasers are an option to encounter these threats. In order to understand their potential in such a scenario, it is vital to investigate the laser effects in the presence of a corresponding aerodynamic environment. Thus, experimental and numerical investigations were conducted cooperatively by Fraunhofer Ernst-Mach-Institut and the Supersonic and Hypersonic Technologies Department of DLR. An ytterbium fiber laser system was installed at the supersonic wind tunnel VMK. The laboratory was fit to meet necessary laser safety requirements. Combined subsonic and supersonic flow and high-power laser experiments with flow velocities up to a Mach number of 3 and a laser power up to 10 kW were realized. Two kind of tests were performed, focusing on laser beam distortion through aero-optical effects and on high-power laser effects, respectively. The interaction effects between aerodynamics, laser radiation and irradiated targets were studied on flatplates as well as cylindrical and radome targets, simulating generic missile design. Irradiated objects consisted of steel, aluminum, carbon-fiber-reinforced polymer and the ceramic-based composite WHIPOX. While beam distortions were studied with a wavefront sensor, damaging processes were investigated by measuring the perforation time of the targets, as well as via high-speed imaging, thermography as well as Schlieren imaging. Numerical three-dimensional, steady, and uncoupled simulations were performed. The data indicated complex interactions between material, laser beam, and aerodynamics. This investigation can be used as an initial basis for further analysis of laser-material-aerodynamic interactions with respect to missile defense.