In this paper, we propose a methodology to acquire and formalize process knowledge for technological innovation and Business Process Re-engineering (BPR). It integrates process modeling and simulation techniques with TRIZ Theory (Russian acronym for Theory of Inventive Problem Solving). The methodology gives the technicians a structured framework, which provides a step-by-step roadmap for BPR through three main phases: acquisition and formalization of AS-IS process knowledge and identification of process criticalities through IDEF techniques, creative problem solving using TRIZ methodology, and modeling and simulation of the new processes, named TO-BE, implementing the new technological solutions. The methodology has been experimented for an industrial test case, permitting us to evaluate its efficacy and benefits.