The hosts, who head the Fifa rankings in the women's game, will be out to impress new coach Tom Sermanni, while striker Abby Wambach is on a mission to overtake Mia Hamm's world record of 158 international goals.
As if that wasn't challenging enough, Scotland's first-choice central defenders Ifeoma Dieke and Rachel Corsie are missing with long-term knee injuries. Influential midfielder Megan Sneddon has also been denied time off by her employers so has not made the trip, which includes a second game in Nashville on Wednesday night.
The Scots lost 8-2 in Ohio in 2002 in the only previous meeting between the teams. Although they have made impressive strides in recent years they face a US side which played 32 matches in 2012, winning 28 of them and losing just one.
In the absence of Dieke and Corsie, Jenny Beattie, the Arsenal striker, is likely to be used as an auxiliary defender to try to contain Wambach. The 32-year-old is just six short of the record set by her compatriot, Hamm, having scored 152 goals for the US.
When the sides last met, Wambach scored the first hat trick of her international career and Hamm scored another. The two games against Scotland, then, present an opportunity to match, or even surpass, her old team-mate's mark.
Sermanni, the Glaswegian who will tonight be in charge of the US team for the first time, would have mixed feelings should Wambach pulled off the feat. "I'll try my best to make sure it doesn't happen against Scotland," he said with a wry smile.
Nevertheless, Sermanni is determined to impress his new employers quickly, with his association still smarting from the 2-1 home defeat by Honduras suffered by the men's team in a opening 2014 World Cup qualifying group game on Wednesday night.
"It wouldn't be a wise decision to start the job by leaving key players on the bench," he said, ahead of a match for which 15,000 tickets have been sold. "From the players' perspective there is a new coach and they will want to play."
That means the Scots are likely to face the side which won the Olympic title by beating World Cup holders Japan at Wembley. Sermanni has taken a meticulous approach to the match, though, and watched a video of Scotland's Euro 2013 play-off defeat against Spain in Madrid for the first time last week.
"Although, obviously, I knew the result I was still really gutted when I saw what happened," he said. "It was hard to believe they were eliminated with the last kick of the ball. Scotland are a decent side who play good football and Anna [Signeul, the head coach] has done a terrific job with them."
The Scots will use these matches as part of their pre-season and Signeul expects her players' lack of match fitness to be reflected in the performance tonight. "We have to acknowledge where we are," she said. "It's about development and helping us set our targets for the future. I want the players to come away from the two games thinking they can be better and striving to be as good as their individual opponents."