In the industrial production scenario, the goal of engineering is focused on the continuous improvement of the process performance by maximizing the effectiveness of the manufacturing and the quality of the products. In order to address these aims, the advanced robust process optimization techniques have been designed, implemented, and applied to the manufacturing process of ultrasound (US) probes for medical imaging. The suggested guideline plays a key role for improving a complex multi-stage manufacturing process; it consists of statistical methods applied for improving the product quality, and for achieving a higher productivity, jointly with engineering techniques oriented to problem solving. Starting from the Six Sigma approach, the high definition of the production process was analyzed through a risk analysis, and thus providing a successful implementation of the PDCA (plan-do-check-act) methodology. Therefore, the multidisciplinary analysis is carried out by applying statistical models and by detecting the latent failures by means of NDT (non-destructive testing), i.e., scanning acoustic microscopy (SAM). The presented approach, driven by the statistical analysis, allows the engineers to distinguish the potential weak points of the complex manufacturing, in order to implement the corrective actions. Furthermore, in this paper we illustrate this approach by considering a pilot study, e.g., a process of US probes for medical imaging, by detailing all the guideline steps.