Anticipating the analysis of cost and performances before the detailed design stage is difficult, but possible thanks to a synthetic analysis of the manufacturing knowledge, a successful collaboration among the numerous actors involved, and a methodology able to highlight the cost issues and to guide a cost-oriented machine design. This paper presents a methodology integrating Design for Manufacturing and Assembly (DFMA), Design To Cost (DTC), and Value Analysis (VA) to support companies in cost-effective machine design and cost-oriented re-engineering. This paper demonstrates the validity of the proposed methodology by an industrial case study focusing on packaging machines, developed in collaboration with a world leader company in tissue packaging machines. Thanks to the proposed approach, the company was able to identify those parts to be re-engineered (e.g., oversized parts, parts with unnecessary tolerances, similar parts to be merged into a unique one, common groups to be reused in similar machines, parts or material substitutions, wrong suppliers' selection) and possible technological improvements. A significant cost optimization and global machine sustainability improvement were achieved on a specific packaging machine line, mainly due to product structure simplification, part reuse, improved design solutions, and optimization of selected manufacturing processes.