After working at Sidley Austin LLP, Vance moved to San Francisco to work in the tech industry as a venture capitalist. He served as a principal at Peter Thiel's firm, Mithril Capital, between 2016 and 2017.
In 2016, Harper published Vance's book, Hillbilly Elegy: A Memoir of a Family and Culture in Crisis. It was on The New York Times Best Seller list in 2016 and 2017. It was a finalist for the 2017 Dayton Literary Peace Prize and winner of the 2017 Audie Award for Nonfiction. The New York Times called it "one of the six best books to help understand Trump's win". The Washington Post called him the "voice of the Rust Belt", while The New Republic criticized him as "liberal media's favorite white trash–splainer" and the "false prophet of blue America." Economist William Easterly, a West Virginia native, criticized the book, writing, "Sloppy analysis of collections of people—coastal elites, flyover America, Muslims, immigrants, people without college degrees, you name it—has become routine. And it's killing our politics."