The build-up to the game has been dominated by speculation about the Manchester United striker, whose club manager David Moyes lost his patience when quizzed about Rooney's future by reporters after Sunday's Community Shield.
The subject of two unsuccessful bids from Chelsea, Rooney has not played in any of United's pre-season games due to hamstring and shoulder injuries, but Hodgson says he is "physically fit" to face the Scots.
Given his lack of match fitness, it seems unlikely that the 27-year-old will be able to manage much more than a cameo, and Hodgson must also show care with some of his other first-team stars.
Frank Lampard, Jack Wilshere and captain Steven Gerrard are all returning after injury, and with the Premier League season beginning on Saturday, avoiding further injuries will be a key consideration.
Wilshere has made just one England start since 2011, brilliantly marshalling the midfield in England's 2-1 defeat of Brazil in February, and Hodgson is delighted to have the Arsenal man at his disposal again.
"I am really pleased he is back with us because he is a precocious talent," said Hodgson.
"His game against Brazil, where he got the man-of-the-match award, still lives long in the memory.
"He was fantastic throughout and I am rather hoping we will get some use from him in qualifying.
"Up to now he has only played the Brazil match and half a match against Sweden (last November) in my time as national-team manager."
Hodgson has only one uncapped player in his squad in 31-year-old Southampton striker Rickie Lambert.
The strapping frontman will hope to make his international debut, and Hodgson may also want to take another look at 20-year-old United newcomer Wilfried Zaha, who made his debut against Sweden last year.
Only Ashley Young, Zaha's new club-mate, has withdrawn from the squad due to injury, ahead of a game that represents a useful staging post in preparation for next month's World Cup qualifiers against Moldova and Ukraine.
Scotland must do without Brighton and Hove Albion midfielder Liam Bridcutt, who has pulled out of the squad due to an apparent groin injury.
Gordon Strachan's side, currently ranked 50th in the world, can no longer qualify for next year's World Cup in Brazil, but they were buoyed by a shock 1-0 win over Croatia in June.
"We have all fed off the result and the performance, but also the reaction at home to it has brought everyone fresh hope that things from this point could improve," said assistant coach Mark McGhee.
Around 20,000 Scottish fans are expected to descend on London for Wednesday's game, which will be the first meeting between the sides since England edged a European Championship play-off in 1999.
The fixture, the oldest in international football, has shaped British football history, from Scotland's 1967 victory over the then world champions at Wembley to England midfielder Paul Gascoigne's famous volley at Euro 96.
The match arrives just over 12 months before next year's referendum on Scottish independence, but McGhee said Strachan would not be fanning any nationalistic flames in his pre-game team talk.
"I think we have got to be scientific about it," he said.
"We have to talk about their players and the problems they are going to give us, talk about their strengths and weaknesses and our strengths and weaknesses and try to find some way of overcoming them.
"I think that will be the focus for Gordon and not the bombastic, 'Flower of Scotland' type of thing.
"Given our recent history, a win would be a fantastic result. Anyone who comes to Wembley and gets anything, regardless of how frustrated England fans may have been at times, have done really, really well."