The importance of design robustness and reliability is a well-established notion and practice in today’s industry. Manufacturing companies strive to achieve Six-Sigma quality measures. While Virtual Prototyping is a key-factor in accelerating the product development process while reducing development costs; it has not contributed in the quest for improved product reliability and robustness performance since it is based on deterministic approaches. This paper provides a systematic approach to design for sixsigma simultaneously addressing variability and uncertainty present in real life on most design parameters. The first step is the ability to flexibly integrate and federate best-of-class virtual prototyping simulation software programs -most based on Finite Element Modeling techniques- thus, capturing existing engineering processes. These engineering processes provide the deterministic calculation engines for assessing design performance outputs of interest, such as -but not limited to- stress, structural impact, eigenfrequencies, forced response functions, fatigue life. Second is the assessment of design parameter variability on the design performance outputs. Analytical methods for the efficient calculation of dynamic response variability examined in this work include reliability-based methods such as First and Second Order Reliability methods, the Importance Sampling Monte Carlo (ISMC) method and the Transformed Importance Latin Hypercube Sampling (TILHS) method. They have been assessed for their ability to accurately predict the failure probability in a reasonable amount of time. The latter criterion is paramount for successful application to large industrial FE models, where the computation time is the main bottleneck. The accuracy has been examined with the comparison of the aforementioned methods with classical and advanced Monte-Carlo methodologies. Uncertainty is treated with the use of Transformation Method based on Fuzzy arithmetic concepts. Fuzzy arithmetic is an attractive mathematical concept to solve problems with uncertain parameters. The Transformation Method (TM) follows a fuzzy approach based on the concept of α-cuts, i.e. discretization of the parameter’s magnitude into a number of intervals. Uncertainty is then assessed by solving the problem in a systematic way: for each combination of the values attained by the uncertain parameters a deterministic computation of the response is performed. In this paper, the TM is demonstrated on an airplane FE model, to assess the effect of material stiffness uncertainty on the FRF from wing tip to pilot seat. A second demonstration example on this model aims to ensure a certain frequency difference between two free-free modes that may result in flutter at certain air speed; several reliability methods are applied for this purpose, namely Monte Carlo simulations, FORM and Importance Sampling.