Here, PA looks at the key issues up for debate.
Can lightning strike three times for Stokes?
Two career-defining performances in the space of six weeks might be enough for most sportsmen, but Ben Stokes will be hungry to add a third. If he can channel the relentless drive and technical brilliance of his knocks in the World Cup final and the third Test at Headingley, he will surely sweep all before him once again. But such performances demand much from those who produce them and is it even reasonable to expect him to deliver again?
Smith versus Archer, round two
The most thrilling contest between bat and ball this summer came when the newly crowned number one batsman in the world, Steve Smith, stared down England debutant Jofra Archer at Lord's. Smith was closing in on a third-successive century when Archer put his foot down in a spell of merciless fast bowling that left Smith floored and on the way to a worrying concussion. After missing the Leeds Test as a result, he is back in action and when Archer gets the ball in hand, it promises to be box office stuff.
Overton in the spotlight
England have sprung something of a surprise by naming Somerset seamer Craig Overton in their XI, taking a role they had previously hoped would go to their record wicket-taker James Anderson. It is a big ask for someone who last appeared on this stage 18 months ago, has lost all three of his previous three Tests and has not been seen in a squad all year before this week. He has enjoyed a profitable season in the championship, with 32 wickets at 21.34 but Australia represents a big step up, and with Chris Woakes and Sam Curran overlooked, he must justify the selectors' faith.
Will the switch be a hit?
Changes to the batting line-up might have been expected after England were skittled for 67 last time out – their second double-figures total of the summer. Although there was no blood-letting from the selectors they did tinker with the order, swapping Jason Roy and Joe Denly. In an ideal world England hope Denly can channel the grittiness that saw him to a chancey half-century in the third Test and join Rory Burns in seeing off the new ball, while simultaneously freeing up Roy to go after the bowlers later in the piece. Sceptics might say it is merely shuffling two players who have yet to prove their Test credentials. How the change goes could be a crucial element over the next five days.
Paine under pressure
Australia captain Tim Paine has been forced to explain away the dropping of Usman Khawaja for lack of runs at number three but in ordinary times it would be his neck on the line. Having taken a poisoned chalice in the aftermath of the sandpaper scandal, he has been given plenty of leeway but he is in dire form with the bat, has not been at his best as a wicketkeeper and openly admits his use of DRS has been shoddy. Win and he would leave Manchester as the first Australian skipper to take the urn home from England in 18 years, but lose and he might find himself on the chopping block before the final match at the Oval.