Toronto (1-1-0) will be down four starters for Sunday's road game against Real Salt Lake (0-0-2), with several reserves also unavailable.
Star midfielder/captain Michael Bradley and striker Jozy Altidore are with the U.S. national team. Starting left fullback Justin Morrow is suspended after losing a red card appeal.
Defender Damien Perquis has recovered sufficiently from a calf injury to play. But fellow centre back Steven Caldwell (calf), and backup defenders Mark Bloom (quad) and Eriq Zavaleta (squad) are out.
Squad player Marky Delgado is away with the U.S. under-23 team.
"I've said all along that I think our team is deep," Vanney said after practice Friday. "And nothing I've seen this week or through pre-season has changed my mind on that.
"Guys understand what their roles are, they understand what we're trying to accomplish. I actually very much look forward to the challenge."
Toronto is likely to start Luke Moore and Collen Warner for Altidore and Bradley, respectively. Ashtone Morgan and Nick Hagglund are expected to step in for Morrow and Caldwell.
Morgan, defender Clement Simonin, midfielder Jay Chapman and striker Jordan Hamilton were called up Friday from Toronto FC 2.
Real Salt Lake, which like Toronto is coming off a bye week, also has roster holes to fill.
The home team will be without goalkeeper Nick Rimando (U.S.), defender Elias Vasquez (Guatemala) and forward Alvaro Saborio (Costa Rica) as well as defender Boyd Okwuonu and midfielder Luis Gil (U.S. under-23).
RSL is still without young designated player Joao Plata, a former TFC attacker who is recovering from a foot injury.
Both teams got a break in that Salt Lake's U.S. international midfielder Kyle Beckerman and Toronto's Italian playmaker Sebastian Giovinco were not called up, however.
Vanney's team will have to fight altitude as well as Real Salt Lake.
RSL, which entered the league in 2005, is 85-32-44 at home — including a 6-1-0 record against Toronto. Compare that to Toronto's home record of 44-40-44 since its arrival in 2007.
RSL has won all six meetings between the teams at Rio Tinto Stadium. The one home loss — a 2-1 decision for Toronto — came July 4, 2007, at Rice-Eccles Stadium in the first meeting ever between the two.
Toronto is not arriving via charter until Saturday — usually it comes in two days before West Coast trips. The idea is to spend as little time as possible at altitude.
"If we are good with the ball and we're efficient in the way we play, it won't be a factor whatsoever," Vanney said of the altitude.
"They're a possession team, they try and make the opposing team run when they come in," added Warner. "It's a difficult place to play but I think we're well equipped to go there and get points."
The game marks a homecoming of sorts for both Warner and forward Robbie Findley. Warner spent his first two seasons there (2011 and 2012) while Findley spent almost all of the last six years in Salt Lake.
Findley says the altitude definitely helps the home side.
"I think it's a big advantage for them," he said. "But I feel this team here has done a lot of fitness ... We've just got to manage the game, go in with our game plan and try to stick to that."
Toronto is coming off a 2-1 loss in Columbus while Real Salt Lake tied visiting Philadelphia 3-3 last time out.
Follow @NeilMDavidson on Twitter