[5] He is best known for contributions to the fields of Systems Engineering, Design optimization, and Space Logistics, where together with colleagues from JPL he coined the term Interplanetary Supply Chain.

[1] His doctoral dissertation titled "Multivariable isoperformance methodology for precision opto-mechanical systems" was supervised by David W. Miller who served as NASA's Chief Technologist.

[6][7] de Weck joined the MIT faculty in 2001 where he has a dual appointment with the Department of Aeronautics and Astronautics and the Institute for Data, Systems, and Society (IDSS).

He previously served on the National Research Council Committee on Cost Growth in NASA Earth and Space Science Missions (2009–2010) and as the Executive Director of the MIT Production in the Innovation Economy (PIE) Study (2010–2013).

de Weck co-authored a book presenting the argument for Engineering Systems as a new discipline: He appears in videos discussing the need for and technical challenges of interplanetary space exploration: and is quoted in media coverage of research to use planetary bodies such as the moon as intermediate in-situ sources of propellants and other resources: He has also published many articles in professional and academic publications such as: