In a declining New England town, the lives of its inhabitants are intertwined by the Knox River and its vacant mills. The story follows Miles Roby, the seemingly content manager of the Empire Grill, who is torn between his principles and his desire to open his own business. His ex-wife Janine, who has developed a selfish attitude, and their teenage daughter Tick, who is struggling with her mother's engagement, are also central characters. The town's wealthiest citizen, Francine Whiting, pulls strings to control the town, while a mysterious suitor, Charlie Mayne, and a symbolsfigure in Miles' life, Max Roby, add depth to the narrative. As the characters' stories unfold, they are all influenced by ghosts of the past and the struggle to find their place in a rapidly changing world.

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Some TV shows that have similar genres and were produced around the same time as Empire Falls include Lessons in Chemistry, Chernobyl, Mad Men, Shardlake, Normal People, Nashville.