The visitors also have Nations League fixtures to keep in mind, but Stephen Kenny's men have performed dismally in the tournament and will be hoping to pull off a monumental shock in midweek.
A clash with an out-of-sorts Ireland side is just what the doctor ordered for Gareth Southgate's England, who will be determined to prove that they have put their pitiful defeat to Denmark behind them ahead of two imperative Nations League showdowns.
No Three Lions fan wants to be reminded of that fateful night in October, which saw Harry Maguire given his marching orders just before the half hour mark, and former Tottenham Hotspur man Christian Eriksen marking his return to the Wembley turf with the winner from 12 yards.
England's bright attacking contingent of Harry Kane, Marcus Rashford, Jadon Sancho and Dominic Calvert-Lewin had no answer to the Danish defence's resolve and Southgate's side suffered their first defeat of the Nations League campaign - with that loss overshadowing England's previous impressive results last month.
The Three Lions swept aside Wales in a friendly before triumphing over Belgium - the number-one ranked team in the world - in Nations League Group A2, but Southgate's men currently sit two points behind the Red Devils ahead of their crunch match this Sunday.
The Three Lions' final group game with Iceland may pale into insignificance depending on the outcome of their encounter with Belgium, and with Southgate sure to go all out this weekend in their bid to make the finals, fans can expect to see a heavily-altered lineup for the visit of Ireland.
Ireland's Nations League campaign has been nothing short of woeful - Kenny's side have not prevailed in any of their four games in Group B4 and are at real risk of relegation heading into the upcoming fixtures.
Only Bulgaria have accumulated fewer points than the Boys in Green, who have drawn two and lost two so far, with Ireland playing out a goalless stalemate with Wales before falling to a 1-0 defeat to Finland last month.
October also saw Ireland's hopes of qualifying for the European Championships dashed as Kenny's men lost their playoff semi-final on penalties to Slovakia, although the Boys in Green do boast a relatively strong friendly record ahead of their trip to Wembley.
Indeed, Ireland are unbeaten in their last five exhibition matches and picked up successive 3-1 victories over Bulgaria and New Zealand in their most recent friendly encounters last year.
Furthermore, history suggests that England's route to victory in this tie may not be that simple - their last six matches with Ireland have ended in draws and the Three Lions last prevailed against their midweek opponents in 1985.
England International Friendlies form: DWWWWW
England form (all competitions): WWDWWL
Republic of Ireland International Friendlies form: LWDDWW
Republic of Ireland form (all competitions): DDLLDL
England's extensive options at right-back are well-documented, but Southgate will be without one man on that side in Trent Alexander-Arnold, who has been forced to withdraw with the calf injury he suffered in Liverpool's draw at Manchester City.
With the hectic fixture schedule taking its toll on players across the globe, Rashford is being assessed after picking up a shoulder problem, but the Manchester United man has joined up with the squad nonetheless.
Tyrone Mings, Bukayo Saka and Jack Grealish are all among those who will be hoping to make the starting lineup here, while Jude Bellingham has also been called up with James Ward-Prowse withdrawing through injury.
Maguire and Reece James are both suspended for the weekend encounter with Belgium, and the defensive duo could therefore be in line for starts here.
However, Joe Gomez is reported to have suffered a serious injury during an England training session, and it remains to be seen how long the Liverpool man may be out of action for.
As for Ireland, Kenny could also shuffle the pack as Ireland look to avoid relegation from their Nations League group, although there will be no David McGoldrick after the Sheffield United man announced his retirement from international duty.
Two Merseyside individuals have been included in the squad, with Everton's Seamus Coleman called up in spite of a hamstring injury, while uncapped Liverpool goalkeeper Caoimhin Kelleher has also linked up with the team.
As is the case with England, Ireland will also be looking to avoid any injury concerns before the Nations League takes centre stage, with youngsters such as Adam Idah, Jayson Molumby and Dara O'Shea all potentially starting here.
However, Sheffield United's Enda Stevens and Brighton & Hove Albion's Aaron Connolly have been forced to withdraw through injury, while West Bromwich Albion forward Callum Robinson has tested positive for coronavirus and will miss out as well.
England possible starting lineup:
Pope; Maguire, Coady, Mings; James, Winks, Rice, Saka; Grealish, Foden; Calvert-Lewin
Republic of Ireland possible starting lineup:
Randolph; Christie, O'Shea, Egan, Long; Molumby, McCarthy, Browne; Horgan, Idah, Brady
We say: England 3-0 Republic of Ireland
Fans can expect to see much-changed starting XI's with England's and Ireland's Nations League fixtures of paramount importance to both managers. The Three Lions have struggled to beat Ireland in recent times, but even with a number of their star attackers rested for this one, Southgate's men should prove too strong for the Boys in Green and we can only see England winning on their own turf.