Here are three keys to watch.
1. Altidore and Wood combine.
Barring a major surprise, U.S. coach Jurgen Klinsmann will start Jozy Altidore and Bobby Wood up front, though it will be only the fourth time they've started together. Usually, one of them has been the target man of the U.S. attack with Dempsey in support behind him.
Wood started at the Copa Centenario in place of the injured Altidore and continued to impress with his finishing in front of goal and ability to physically punish defenders. In many ways, he is similar to Altidore, though more mobile and perhaps more efficient with his chances.
Wood and Altidore are only started in three games over the last years, mostly recently in the 6-1 win over the Vincy Heat to open World Cup qualifying in last November.
Wood had the tying goal after the USA fell behind on Oalex Anderson's goal after five minutes, while Altidore later added two goals to give him five in the three games he's started alongside Wood.
2. Who will replace Bradley and Jones in midfield?
Bradley and Jones was Klinsmann's starting central midfield for five of the six games at the Copa Centenario and for the first two games of World Cup qualifying.
With Jones suspended for the next two games in March, Klinsmann first started Mix Diskerud alongside Bradley and when that didn't work out Kyle Beckerman for the second of the back-to-back games against Guatemala. Beckerman struggled in his only start at the Copa Centenario -- the 4-0 to Argentina -- but get the start on Friday.
Like Jones, Alejandro Bedoya started all but the Argentina game at the Copa Centenario and will surely start on Friday. He can play in the middle or outside, giving Klinsmann the option of finding starting Darlington Nagbe.
3. USA must avoid repeat of Antigua & Barbuda game.
Klinsmann's message to his players is play with urgency and take care of business.
Four years ago, the USA played a similar game on Day 5 of the semifinal round: an away game against a Caribbean minnow -- Antigua & Barbuda -- played at a cricket ground -- Sir Vivian Richards Stadium -- in a must-win situation with just seven points after four games.
The USA traded goals with Antigua & Barbuda in the first half and waited until the 90th minute to get the winner from Eddie Johnson for a 2-1 victory.
The USA is a deeper team than it was four years and St. Vincent & the Grenadines isn't as good as Antigua & Barbuda, but the game is a cautionary tale.
A win would make for a tense couple of hours as the USA awaited the result of the game later in the day in Trinidad & Tobago, where the Soca Warriors would send themselves and the USA into the Hexagonal with a win over Guatemala.
GOALKEEPERS (3): Brad Guzan (Middlesbrough/ENG), Ethan Horvath (Molde/NOR), Tim Howard (Colorado Rapids).
DEFENDERS (7): Kellyn Acosta (FC Dallas), Matt Besler (Sporting KC), Steve Birnbaum (D.C. United), Geoff Cameron (Stoke City/ENG), Omar Gonzalez (Pachuca/MEX), Fabian Johnson (Borussia Moenchengladbach/GER), *DeAndre Yedlin (Newcastle United/ENG).
MIDFIELDERS (8): Paul Arriola (Tijuana/MEX), Kyle Beckerman (Real Salt Lake), Alejandro Bedoya (Philadelphia Union), Darlington Nagbe (Portland Timbers), Sacha Kljestan (NY Red Bulls), Christian Pulisic (Borussia Dortmund/GER), Caleb Stanko (FC Vaduz/LIE), Graham Zusi (Sporting KC).
FORWARDS (5): Jozy Altidore (Toronto FC), Jordan Morris (Seattle Sounders), Rubio Rubin (FC Utrecht/NED), Chris Wondolowski (San Jose Earthquakes), Bobby Wood (Hamburg/GER).
*Carrying yellow cards.