Nesmith missed Saturday's 69-50 loss to Texas A&M, and Stackhouse said afterward the injury will keep the sophomore guard using a scooter for much of the next six weeks.
It marks a second straight season that Vanderbilt has lost its best player and projected first-round pick to an injury. The Commodores lost freshman Darius Garland, now in the NBA with Cleveland, to a knee injury after five games last season.
"We don't anticipate him being a part of what we're doing anymore this season,'' Stackhouse said of Nesmith.
Nesmith ranked fifth nationally averaging 23 points a game and played an average of 36 minutes a game. Stackhouse said Nesmith's foot had been checked by X-rays, but an MRI after an 83-79 loss at No. 5 Auburn showed the unspecified injury.
Stackhouse said Nesmith was in tears after learning the diagnosis. Nesmith watched from the bench forced to use a scooter to keep his weight off his right foot protected by a walking boot. Stackhouse said no ligaments were involved.
In his latest mock draft, ESPN's Jonathan Givony had Nesmith going 22nd overall in June's NBA draft.
Texas A&M coach Buzz Williams learned of Nesmith's injury at a morning shootaround, not enough time to make adjustments. None were needed as Jay Jay Chandler added 10 point, and the Aggies never trailed in winning their second straight.
"I hate it for him because I've known him forever, and I think he's a really good person and a really good player,'' Williams said.
Nesmith had been one of only two players nationally to make seven or more 3s in a game four times this season as a 52.2% shooter outside the arc, and he had been Vanderbilt's best scorer in a half century since Tom Hagan averaged 23.4 points a game in the 1968-69 season.
Without Nesmith, Stackhouse started Saben Lee who had been coming off the bench this season. Stackhouse also was forced to play three walk-ons. Braelee Albert arrived on campus in December but was on the court in the first half with Jon Jossell, a manager the past three seasons. Junior walk-on Isaiah Rice got on the floor in the second half.
"It was the perfect storm for us tonight,'' Stackhouse said. "Not what we wanted to see with a team that was trying to find some continuity with some lineups and different things we had't had to use before.''
The Associated Press contributed to this report.