While some of the novel occurs in England, and the central characters are European, Death on the Nile is set mainly in Egypt in the late 1930s. When the novel was published, travel abroad to Egypt was fashionable among wealthy Europeans, especially given contemporaneous discoveries in Egyptology. As a result, a mystery novel set in Egypt would be especially appealing to English-language readers. Europeans, and especially the British, had a relatively easy time traveling to Egypt at this time. The construction of the Suez Canal in 1862 eased passage into the area considerably, and the British controlled Egypt from 1882 to 1956. Christie incorporates impressive and tone-setting elements such as menacing statues, ancient temples, and of course the Nile River, which the characters travel down by means of the steamer Karnak.
The murder and ensuing investigation take place on the boat, which is crucial to the plot: the characters are trapped together, and there are a limited number of suspects to question. Additionally, the enclosed crime scene means that many passengers were nearby when Linnet's murder occurred, and therefore Poirot has more success finding witnesses and clues. Christie employs the same setting device in Murder on the Orient Express, in which the crime and investigation occur on a train the characters cannot leave.