Optimization studies for nonlinear constrained problems (i.e. most complex engineering design problems) have repeatedly shown that (i) no single optimization technique performs best for all design problems, and (ii) in most cases, a mix of techniques perform better than a single technique for a given design problem. iSIGHT TM is a generic software framework for integration, automation, and optimization of design processes that has been developed on the foundation of interdigitation: the strategy of combining multiple optimization algorithms to exploit their desirable aspects for solving complex problems. With the recent paradigm shift from traditional optimization to design space exploration for evaluating “what-if” scenarios and trade-off studies, iSIGHT has grown from an optimization software system to a complete design exploration environment, providing a suite of design exploration tools including a collection of optimization techniques, design of experiments techniques, approximation methods, and probabilistic quality engineering methods. Likewise, the interdigitation design methodology embodied in iSIGHT has grown to support the interdigitation of all design exploration tools for effective design space exploration. In this paper we present an overview of iSIGHT, past and present, of the interdigitation design methodology and its implementation for multiple design exploration tools, and of an industrial case study for which elements of this methodology have been applied.