During her doctorate O'Reilly worked as a graduate fellow at the Santa Fe Institute.

[1] She joined the MIT Computer Science and Artificial Intelligence Laboratory as a postdoctoral fellow in 1996.

[2] O'Reilly is a principal research scientist at the MIT Computer Science and Artificial Intelligence Laboratory, where she leads a team focusing on scalable machine learning.

[1][4] O'Reilly has designed computational models for a variety of different problems, including calculating the financial risk of renewable energy investments and creating a flavor algorithm that replaces taste testers.

[5] O'Reilly has developed statistical models to inform the design of renewable energy systems, including predicting wind speed.