The plot revolves around an agoraphobic architect and mother named Bernadette Fox, who goes missing prior to a family trip to Antarctica.

15-year-old Bee Branch lives in Seattle with her father Elgin, a computer genius who works for Microsoft, and mother Bernadette, an agoraphobic stay-at-home parent.

Bernadette delegates the task of making their arrangements to a personal assistant in India named Manjula, and has ongoing feuds with some of the other mothers at Bee's private school, the main instigator being their neighbor Audrey Griffin.

Bee's parents had previously promise her a reward of her choosing in exchange for good grades - upon presenting them with a perfect report card, she requests a family vacation to Antarctica.

This caused Bernadette to lose her creative passion and prompted her relocation to Seattle, where she suffered four miscarriages before becoming pregnant with Bee.

Elgin stages an intervention at their home with the FBI and police present, in the midst of which Bernadette excuses herself to go to the bathroom, but does not return.

While there, she met a scientist who told her about Palmer Station and an architectural project for the South Pole in which every material would have to be shipped from the U.S. Bernadette snuck on board Palmer Station hoping to work on the project and sent the letter to Bee asking for her blessing and promising to return home if she did not get it within a set period of time.