Medvedev has won 23 of his past 26 matches, with 19 of his triumphs during that run has come in straight sets.
The Russian will play against Novak Djokovic, Stefanos Tsitsipas and Casper Ruud in the Green Group.
Zverev, who famously won the 2018 Nitto ATP Finals title, will compete at the season finale for the fifth straight year.
The Serbian went 27-1 in major championships this year, winning titles at the Australian Open, Roland Garros and Wimbledon.
The 20-year-old Jannik Sinner is in with an outside chance of making the ATP Finals. But his 2021 season has been excellent regardless.
The ATP Finals 2021 will close out the men's tennis season at the end of the year and so far, only three of the eight spots in the tournament have been filled.
On the back of winning his sixth Wimbledon title and 20th Grand Slam crown, Novak Djokovic secured his 14th qualification for the season finale.