The outdated and oversized nuclear manufacturing complex within the United States requires its transformation into a smaller, safe, and secure enterprise. Health and safety risks, environmental concerns, and the end of the Cold War have all contributed to this necessity. The events of September 11, 2001, emphasized the protection requirements for nuclear materials within the U.S. as well as abroad. Current Nuclear Safeguards regulations contain minimal prescriptive requirements relating to the design of new production facilities. Project management and engineering design guides require that design documents contain specific and measureable statements relating to systems requirements. The systems engineering process evaluates alternatives for an effective and integrated solution during project design. A Safeguards Design Strategy for domestic nuclear materials processing facilities based upon a core "framework" of safeguards regulatory programmatic elements that also use the prescriptive requirements and similar goals of safety, health, and physical security regulations is proposed and justifiable.