The plastic industry is undergoing drastic changes, due to the customer sustainability perception of plastics, and the eruption of new processes (such 3D printing) and materials (such as renewably sourced resins). To enable a fast transition to high-quality, sustainable plastic applications, a specific methodology could be a key competitive advantage. This novel methodology is focused on improving the objectivity and efficiency of plastic production and the design review process. It is applicable to discrete optimization events in any product lifecycle milestone, from concept design to serial production stages. The methodology includes a natural way to capture plastic-related knowledge and trends, oriented towards building a dynamic “interaction matrix”, with a list of potential optimizations and their positive or negative impacts in a comprehensive set of multi-criteria evaluations. With an innovative approach, the matrix allows the possibility to incorporate a business strategy, which could be different at every lifecycle stage. The business strategy is translated from the common “verbal” definition into a quantitative set of “Target and Restrictions”, making it possible to detect and prioritize the best potential design optimization changes according to the strategy. This methodology helps to model and compare design alternatives, verify impacts in every evaluation criteria, and make robust and objective information-based decisions. The application of the methodology in real cases of plastic material design optimization in the automotive industry has provided remarkable results, accelerating the detection of improvement methods aligned with the strategy and maximizing the improvement in product competitiveness and sustainability. In comparison with the simultaneous application of existing mono-criteria optimization methodologies (such as “Design to Cost” or “Eco Design”) and subjective expert-based reviews, the novel methodology has a reduced workload and risks, confirming its potential for future application and further development in other polymer-based products, such as consumer goods or packaging.