Wales go head-to-head with England on October 8 in a warm-up game for their Nations League fixtures against Belgium and Denmark.
The Three Lions recorded a narrow 2-1 victory in the last meeting between the two teams at the 2016 European Championships.
England have won five-in-a-row against Wales since being defeated by a Mark Hughes goal back in 1984 and are favourites in the latest football betting to enhance that record at Wembley Stadium.
Read on as we take a look at the main talking points from the respective squad announcements and assess which team will come out on top.
Bale Blow for Wales
Wales boss Ryan Giggs has left Gareth Bale out of his squad, although he expects the Tottenham Hotspur forward to return to action soon.
Bale suffered a knee injury on international duty during September and is yet to play for Spurs after re-joining the club on loan from Real Madrid.
Giggs confirmed that he spoke with Bale and the medical team about the issue and they had agreed to give him more time to recover.
The 31-year-old is expected to play for Spurs against West Ham United on October 17 and should be back in the Wales squad next time around.
Ramsey Returns After Injury
Aaron Ramsey has returned to the Wales squad after missing the Nations League fixtures against Finland and Bulgaria in early September.
The Juventus midfielder is an important player for Wales, having scored 16 goals in 60 appearances for the national team.
Ramsey has been in impressive form for Juve during the early part of the season, and his return to the squad is a big boost for Giggs.
The 29-year-old has the ability to trouble England’s backline and could be worth an interest in the ‘score any time’ market.
Calvert-Lewin Handed Chance to Shine
Dominic Calvert-Lewin has been called up to the England senior squad for the first time following a blistering start to the 2020/21 campaign.
The Everton striker has scored eight goals in five appearances in all competitions so far this season, including two hat-tricks.
The 23-year-old has looked much improved under manager Carlo Ancelotti and will be eager to transfer his form onto the international stage.
Calvert-Lewin bagged seven goals in 17 appearances at U21 level and now looks ready to make his mark with the senior team.
Youngsters Given Time to Reflect
Mason Greenwood and Phil Foden have been left out of the squad as punishment for a breach of discipline during the recent visit to Iceland.
The pair were sent home for mixing outside the enforced ‘bubble’ around the squad having made their senior debuts in the Nations League clash earlier the same day.
Greenwood and Foden later apologised for their behaviour, but manager Gareth Southgate has decided to give them additional time to reflect on their actions.
However, the England manager has confirmed that they will come back into contention for selection for England’s international games in November.
Wales Keen to Continue Good Run
England looked short of their best in their Nations League matches during September and will be eager to step things up against Wales.
Gareth Southgate’s team looked particularly short of ideas against Denmark and they will need to show much more creativity at Wembley.
Wales are now unbeaten in their last eight internationals and will fancy their chances of frustrating the Three Lions.
However, with Bale currently out of the equation they could find it difficult to break down England’s defence.
Goalkeepers: Jordan Pickford (Everton), Nick Pope (Burnley), Dean Henderson (Manchester Utd).
Defenders: Trent Alexander-Arnold (Liverpool), Ben Chilwell (Chelsea), Conor Coady (Wolverhampton Wanderers), Eric Dier (Spurs), Joe Gomez (Liverpool), Michael Keane (Everton), Harry Maguire (Man Utd), Ainsley Maitland-Niles (Arsenal), Tyrone Mings (Aston Villa), Bukayo Saka (Arsenal), Kieran Trippier (Atletico Madrid), Kyle Walker (Manchester City).
Midfielders: Jordan Henderson (Liverpool), Jack Grealish (Aston Villa), Mason Mount (Chelsea), Kalvin Phillips (Leeds United), Declan Rice (West Ham United), James Ward-Prowse (Southampton), Harry Winks (Spurs).
Forwards: Tammy Abraham (Chelsea), Harvey Barnes (Leicester City), Dominic Calvert-Lewin (Everton), Danny Ings (Southampton), Harry Kane (Spurs), Marcus Rashford (Man Utd), Jadon Sancho (Borussia Dortmund), Raheem Sterling (Man City).
Goalkeepers: Wayne Hennessey (Crystal Palace), Danny Ward (Leicester), Adam Davies (Stoke City).
Defenders: Chris Gunter (Unattached), Ben Davies (Spurs), Connor Roberts (Swansea City), Ethan Ampadu (Sheffield United), Chris Mepham (Bournemouth), Joe Rodon (Swansea), Neco Williams (Liverpool), Ben Cabango (Swansea), Rhys Norrington-Davies (Luton Town).
Midfielders: Aaron Ramsey (Juventus), Jonathan Williams (Charlton Athletic), Harry Wilson (Liverpool), David Brooks (Bournemouth), Joe Morrell (Bristol City), Will Vaulks (Cardiff City), Matthew Smith (Man City), Brennan Johnson (Lincoln City), Daniel James (Man Utd), Dylan Levitt (Man Utd).
Forwards: Hal Robson-Kanu (West Bromwich Albion), Kiefer Moore (Cardiff), Tyler Roberts (Leeds), Rabbi Matondo (Schalke 04), Ben Woodburn (Oxford United).