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This paper explores a cyber-physical systems (CPS) approach to optimize the design of rigid, low-rise structures subjected to wind loading. The approach combines the accuracy of physical wind tunnel testing with the ability to efficiently explore a solution space using numerical optimization algorithms. The approach is fully automated, with experiments executed in a boundary layer wind tunnel (BLWT), sensor feedback monitored by a computer, and actuators used to generate physical changes to a mechatronic structural model. The approach was demonstrated for a low-rise structure with a parapet wall of variable height. A non-stochastic optimization algorithm was implemented to search along the domain of parapet heights to minimize both positive and negative pressures on the roof a of a 1:18 length scale low-rise building model. Experiments were conducted at the University of Florida Experimental Facility (UFEF) of the National Science Foundation’s (NSF) Natural Hazard Engineering Research Infrastructure (NHERI) program.