The novel takes place mostly in New York City, shortly after terrorists destroy the Twin Towers in 2001. However, the time switches from the narrator's present to the late 1940s when his grandparents are newlyweds and even farther back to when they are teenagers in Germany.

In the present time, Oskar lives in an apartment building. Across the street, in another building, is his grandmother. The two of them sometimes communicate with one another through signs in their windows and walkie-talkies.

Oskar roams all over the city, especially in his search for the owner of the key he has discovered in his father's closet. He is only nine years old, but he travels in taxis, knocks on strangers' doors, and visits every borough in New York. Oskar is afraid of riding on the subway because the subway is considered a viable target for another terrorist attack. Oskar is afraid of suffering the same fate as his father.

The other location frequented, through the stories of Oskar's grandparents, is Dresden, Germany. Both grandparents lived in Germany as children. When they were teens, Dresden was severely bombed by the Allied Forces during World War II. Both grandparents lost their entire families. Oskar's grandfather was severely burned. He also lost his pregnant girlfriend, Anna, Oskar's grandmother's older sister. His trauma was intensified when he was forced to kill escaped zoo animals. This lifelong regret explains why he keeps so many animals in his apartment. His other traumas make his refusal to talk about his emotions understandable. He is afraid to love because he is afraid of getting hurt.