In this work the problem of calibrating Flush Air Data Sensing (FADS) has been addressed. The inverse problem of extracting freestream wind speed and angle of attack from pressure measurements has been solved. The aim of this work was to develop machine learning and statistical tools to optimize design and calibration of FADS systems. Experimental and Computational Fluid Dynamics (EFD and CFD) solve the forward problem of determining the pressure distribution given the wind velocity profile and bluff body geometry. In this work three ways are presented in which machine learning techniques can improve calibration of FADS systems. First, a scattered data approximation scheme, called Sequential Function Approximation (SFA) that successfully solved the current inverse problem was developed. The proposed scheme is a greedy and self-adaptive technique that constructs reliable and robust estimates without any user-interaction. Wind speed and direction prediction algorithms were developed for two FADS problems. One where pressure sensors are installed on a surface vessel and the other where sensors are installed on the Runway Assisted Landing Site (RALS) control tower. Second, a Tikhonov regularization based data-model fusion technique with SFA was developed to fuse low fidelity CFD solutions with noisy and sparse wind tunnel data. The purpose of this data model fusion approach was to obtain high fidelity, smooth and noiseless flow field solutions by using only a few discrete experimental measurements and a low fidelity numerical solution. This physics based regularization technique gave better flow field solutions compared to smoothness based solutions when wind tunnel data is sparse and incomplete. Third, a sequential design strategy was developed with SFA using Active Learning techniques from the machine learning theory and Optimal Design of Experiments from statistics for regression and classification problems. Uncertainty Sampling was used with SFA to demonstrate the effectiveness of active learning versus passive learning on a cavity flow classification problem. A sequential G-optimal design procedure was also developed with SFA for regression problems. The effectiveness of this approach was demonstrated on a simulated problem and the above mentioned FADS problem.