Set in a fictional prairie town in which the two overarching industries are a living history facility and a laboratory for experiments in high-energy particle physics, Charmed Particles tells the intertwined stories of two families.

Abhijat is a theoretical physicist from India now working at the National Accelerator Research Laboratory. His wife, Sarala, home with their young daughter, Meena, struggles to assimilate to their new American culture.

Meena's best friend at school is Lily, a precocious child prodigy whose father self-identifies as "the last great gentleman explorer” and whose mother, a local politician, becomes entangled in efforts to stop to the National Accelerator Research Laboratory's plans to build a new superconducting supercollider.

The conflict over the collider fractures the community and creates deep divides within the families of the novel.