At its core, The Fountain is the story of a 21st century man, Tom, (Hugh Jackman), losing his wife Izzi (Rachel Weisz) to cancer in 2005. As she is dying, Izzi begs Tommy to share what time they have left together, but he is focused on his quest to find a cure for her.
While he's working in the lab, she writes a story about 16th century Queen Isabella losing her territory to the Inquisition while her betrothed, conquistador Tomás, plunges through the Central America forest in Mayan territory, searching for the Tree of Life for his Queen.
Since she doesn't have time herself, Izzi asks Tommy to finish the story for her. As they look out to the stars, she imagines that their souls will meet there when the star dies. And we see astronaut Tom, in 2500, traveling there for the event, in a spaceship made of an enclosed biosphere containing the Tree of Life.
The three story lines are told nonlinearly, each separated by five centuries. The three periods are interwoven with match cuts and recurring visual motifs; Hugh Jackman and Rachel Weisz play the main characters for all three narratives. Even within a given narrative, the elements of that particular story are not told in chronological order.