Although the two main characters in A Dream of Annapurna are Italian and the novel is set partly in Tuscany, in many ways this is an international novel, with people from France, Italy, America, Russia, Switzerland, Spain, China, and Nepal playing small but important parts in the story. The settings, too, range from Italy to New York, Paris to Kathmandu, and the lower slopes of Annapurna. The novel is both historical and contemporary, spanning a period of sixty years, from 1955 to 2015, and combining both real-life and fictional characters.

The major themes of the novel are universally human and include youth, ambition, age, friendship, fear, bravery, and love. Overshadowing these human characteristics is an implacable natural world. The mighty mountain Annapurna, long the focus of the protagonists' dreams, comes to loom physically over them, but even the permanence of the natural world is threatened by the horrific earthquake which hit Kathmandu on 25 April 2015.