The Three Lions are already guaranteed to miss out on a place at the Nations League finals, while Roberto Mancini's side sit three points better off.
Match preview
The Azzurri faithful will not be booking any holidays to North Macedonia anytime soon, as the reigning champions will be forced to watch the 2022 World Cup from home after succumbing to a 1-0 playoff defeat to the world's 64th-ranked nation.
From storming to continental glory at Wembley in 2021 to failing to qualify for the biggest tournament of them all for the second consecutive time, Italy won 15 games in a row up until last summer - they have now posted just four wins from their last 14 in all tournaments.
Taking five points from their opening three Nations League clashes was a far from disastrous way to start proceedings, but Mancini's side were torn to shreds in a 5-2 defeat to Germany during their most recent game, which leaves them languishing in third place in the standings.
Qualification for the finals is still within the Azzurri's reach, with the European champions seeking to improve on their third-placed Nations League finish in 2020-21, but the previously steadfast Italian defence have now gone six games without a clean sheet at home.
Only once have the hosts failed to score in a Nations League game on Italian turf, though, and the consolation of Nations League qualification may help Mancini and co get through their November friendlies with fellow Qatar absentees Albania and Austria that little bit easier.
Germany's 5-2 win over Italy would likely have made back-page headlines on any other day, but England's 4-0 drubbing at the hands of Hungary unsurprisingly dominated talk of the Nations League in June, as Gareth Southgate's men were well and truly humbled at Molineux.
Some fans quickly pointed the finger of blame at the organisers for scheduling four international fixtures in quick succession after a gruelling domestic campaign, as the Three Lions suffered their heaviest home defeat in 94 years to send them to the bottom of the pile.
Still without a win in the 2022-23 Nations League, the Euro 2020 runners-up mathematically cannot finish first in League A Group 3 and only have the one goal to boast from their opening four games - no other team in League A have been as profligate as England.
Unlike their upcoming hosts, England do have a World Cup to prepare for as they warm up for clashes with Iran, Wales and the USA in Group B, but optimism will not be at its highest point in November if the Three Lions are to exit the Nations League with a whimper.
England and Italy butted heads in front of a youthful Molineux crowd back in June, with only children and their guardians permitted to attend following the disgraceful scenes of crowd disorder at Euro 2020, but the two continental giants could only play out a drab goalless stalemate.
Italy Nations League form:
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Italy form (all competitions):
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England Nations League form:
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England form (all competitions):
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Team News
Italy have already lost a trio of experienced players to injury for September's games, as Lorenzo Pellegrini and Matteo Politano have been forced to withdraw alongside Marco Verratti. Davide Frattesi and Manolo Gabbiadini have been called up as replacements.
Mancini controversially decided against calling up Davide Calabria and Nicolo Zaniolo for September's fixtures, while Leeds United's Wilfried Gnonto and West Ham United's Gianluca Scamacca have both made the cut.
A distinct lack of options out wide should benefit Gnonto's chances of starting, especially after the 18-year-old scored against Germany last time out, but Scamacca will likely take a back seat as Ciro Immobile seeks his first international goal in 15 months.
As for England, Southgate's ever-criticised squad selection saw a maiden call-up for Brentford striker Ivan Toney, but 50-goal captain Harry Kane ought to lead the line from the off as he closes in on Wayne Rooney's record of 53 strikes for the Three Lions.
Kalvin Phillips has been forced to withdraw due to a shoulder injury which could threaten his participation at the World Cup; Jordan Henderson has been called up in his place but should be kept in reserve having just come back from his own hamstring injury.
The absence of number one Jordan Pickford should allow Aaron Ramsdale to prove his worth to Southgate this week, while John Stones will serve a suspension following his sending-off against Italy, and teammate Kyle Walker may not be risked either given his recent injury.
Italy possible starting lineup:
Donnarumma; Di Lorenzo, Bastoni, Bonucci, Emerson; Barella, Tonali, Jorginho; Gnonto, Immobile, Grifo
England possible starting lineup:
Ramsdale; James, Tomori, Maguire; Trippier, Rice, Bellingham, Chilwell; Sterling, Kane, Foden
We say: Italy 1-1 England
Both Italy and England are a far cry from where they were at Euro 2020, so Southgate and Mancini ought to feel that their opposite number is there for the taking this week, and the hosts can play with the handbrake off given their lack of World Cup commitments.