England's meeting with their oldest and fiercest rival - which is being played to commemorate the 150th anniversary of the first international between the nations on 30 November 1872 - is their first friendly in 18 months, since the back-to-back wins over Switzerland and the Ivory Coast in March 2022.
Southgate faced criticism for his sticking with senior players Jordan Henderson, who is now playing in Saudi Arabia, and out-of-favour Manchester United defender Harry Maguire in Saturday's 1-1 draw with Ukraine in Euro 2024 qualifying but he was expected to make changes against the Scots.
But the England manager says he "can't fiddle around" with the team against Steve Clarke's in-form side, who could become the first nation to reach next summer's Euros if other results go their way on Tuesday.
"We've got to find the right balance of physical freshness - we've had a day less preparation - experience, finding out about some players, winning, playing well: the usual things that are expected of us with England, really," Southgate said.
"But the first thing is we can't fiddle around with the team because we're playing a top-level side who will be at full-tilt and giving us a really high-level challenge. You can't overly experiment because that would be ridiculous."
However, Southgate acknowledged that the occasion would give him the opportunity to "find out a bit more" about the characters of some of his less experienced players, raising the possibility that the likes of Levi Colwill or Eberechi Eze could feature.
Southgate added: "We see it as a really good test of us as a team. We'll learn a lot about the group and individuals within it. We're playing a really high-level opponent in an intimidating atmosphere and they're the sorts of nights that have been an important part of our progress.
"Some players will have experienced that, some won't. It's going to be great to find out a bit more about them. We've got to compete, we'll get rolled over if we don't compete."
England had breezed through qualifying with four wins from as many games, including against Italy in Naples, before being held by Ukraine in Wroclaw.
The result has led to familiar criticism of Southgate's tactics and selections but he brushed aside the questions and said the scrutiny on him will never end.
"We weren't as happy coming away with a point as we might have been," Southgate said. "It's still a really good result and we saw what happened in our group later in the night.
"When we beat North Macedonia, people were questioning the quality they had and the standard of the opposition but Italy went there and couldn't get a win so we we kind of know the cycle frankly with England.
"I've been in the job long enough now. It's constant, it's never-ending. But we have to really focus internally on what's important for us, review to our own standards and know what we're working towards and comparing ourselves to, really."