1962. A glamorous American couple, the charismatic Chester MacFarland (Mortensen) and his alluring younger wife Colette (Dunst), arrive in Athens by boat via the Corinth Canal. While sightseeing at the Acropolis they encounter Rydal (Isaac), a young, Greek-speaking American who is working as a tour guide, scamming tourists on the side. Drawn to Colette's beauty and impressed by Chester's wealth and sophistication, Rydal gladly accepts their invitation to dinner. However, all is not as it seems with the MacFarlands and Chester's affable exterior hides darker secrets. When Rydal visits the couple at their exclusive hotel, Chester presses him to help move the body of a seemingly unconscious man who he claims attacked him. In the moment, Rydal agrees but as events take a more sinister turn he finds himself compromised and unable to pull himself free. His increasing infatuation with the vulnerable and responsive Colette gives rise to Chester's jealousy and paranoia, leading to a tense and dangerous battle of wits between the two men.

Frances Mayes is a San Francisco-based literature professor, literary reviewer and author, who is struggling in writing her latest book. Her outwardly perfect and stable life takes an unexpected turn when her husband files for divorce. He wants to marry the woman with whom he is having an affair. Frances supported her husband financially as he was writing his own book, and he sues her for alimony despite her financial difficulties. And he wants to keep the house. Frances eventually accepts her best friend Patti's offer of a vacation, a gay tour of Tuscany which Patti and her lesbian partner Grace originally purchased for themselves before Patti found out that she is pregnant. The gift is a means to escape dealing with the divorce, from which Patti feels Frances may never recover emotionally without some intervention. Feeling that Patti's assessment may be correct in that she has too much emotional baggage ever to return to San Francisco, Frances, while in Tuscany, impulsively ditches the tour to purchase an aged villa, which ends up being a fixer-upper. Frances has many obstacles in eking out a productive and happy life in her new surroundings, that happy life which she hopes will eventually include rediscovering romantic love. In a discussion with sympathetic real estate agent Signor Martini, Frances outlines what emotionally she wants to accomplish with the villa, despite none of those items in a substantive material sense currently being in her life. In response, Martini tells her the story of a set of railroad tracks that were laid between Vienna and Venice before an engine that could make the trek being built, a train which now regularly travels the route. The question becomes whether Frances, in going through the process, will be laying another Vienna to Venice track, and if so whether that end product emotionally will be exactly as she envisions.