Both won their opening Group B fixture, so one more point should prove enough for the reigning champions and their Nations League nemesis to progress.
Match preview
When Spain coach Luis de la Fuente sent his side out at Berlin's Olympiastadion for their Euro 2024 opener, he could scarcely have dreamed they would return at half time with a three-goal lead over Croatia.
Alvaro Morata, Fabian Ruiz and Dani Carvajal all scored before the break to start the campaign with a resounding success, as Morata made it into double figures from his 15 major tournament appearances and Carvajal became the oldest Spanish scorer at a Euros.
Having also fielded the competition's youngest player - 16-year-old Lamine Yamal, creator of La Roja's third goal - and seen Unai Simon save a spot-kick, a composed performance suggests they could be challengers for the trophy this summer.
European champions in 1964, 2008 and 2012, Spain's hopes of adding a fourth continental crown to their collection are high, as they have now lost just one of 11 competitive games under De la Fuente, winning each of the last seven.
That represents their best run since 2017, and recent results against their next opponents in the so-called 'Group of Death' have been particularly positive.
La Roja beat Italy in successive UEFA Nations League semi-finals, going on to win last year's edition for good measure - but they have never before won three consecutive matches against their Italian rivals.
When the two teams meet in Gelsenkirchen, a point apiece may be enough to see both through to the last 16 - potentially allowing De la Fuente to rest key players against Albania - but plenty of pride will still be at stake.
While their Iberian counterparts have held the upper hand of late, Italy memorably overcame Spain on penalties three years ago, en route to Euro 2020 glory.
Since losing to La Roja in the Nations League last June, the new-look Azzurri have been beaten in only one of their next 12 matches - winning eight - and Luciano Spalletti has brought renewed vigour to a squad that had started to falter under Roberto Mancini.
However, Italy started the defence of their title in the worst possible fashion, before quickly recovering from an early blow in Saturday's Group B clash against Albania to take maximum points.
Sassuolo's Nedim Bajrami set a new Euros record for fastest goal ever - netting after just 23 seconds - but Spalletti's side soon bounced back: Alessandro Bastoni levelled the scores 10 minutes later, before his Inter Milan teammate Nicolo Barella put them ahead.
Now unbeaten in 10 games at the European Championship - with the first match of that run being a 2-0 win over Spain in 2016 - Italy's last defeat in the competition came against the Republic of Ireland eight years ago.
Though considered outsiders this summer, the Azzurri's ultimate ambition is become just the second team to win successive Euros, following in the footsteps of Spain. First, though, they must make sure of progress to the knockout phase.
Spain European Championship form:
W
Spain form (all competitions):
W
L
D
W
W
W
Italy European Championship form:
W
Italy form (all competitions):
D
W
W
D
W
W
Team News
Assuaging concerns about their fitness following last week's win over Croatia, both Rodri and Alvaro Morata have taken part in full training and will be available on Thursday, when Aymeric Laporte could make his return from injury.
The France-born defender missed Spain's opening match entirely but may now take a place on the bench, with Nacho and Robin Le Normand continuing in the centre of La Roja's back four.
Few changes - if any - are expected to Luis de la Fuente's lineup, though Dani Olmo and Alex Grimaldo front a long queue for promotion to the starting XI.
Meanwhile, Italy can also name an unaltered side in Gelsenkirchen, as all of their players were available for training following the victory over Albania.
Luciano Spalletti has claimed he is not tied down to a particular formation, but some personnel changes would indicate a more cautious approach: Gianluca Mancini offers a more conservative centre-back option than forward-raiding Riccardo Calafiori; Bryan Cristante could replace Roma teammate Lorenzo Pellegrini to tighten up the Azzurri's midfield.
One man certain to start is Nicolo Barella, who has now posted five goal involvements from his last seven international appearances, but Genoa striker Mateo Retegui is pushing to displace Gianluca Scamacca up front.
Spain possible starting lineup:
Simon; Carvajal, Le Normand, Nacho, Cucurella; Pedri, Rodri, Ruiz; Yamal, Morata, Williams
Italy possible starting lineup:
Donnarumma; Di Lorenzo, Bastoni, Calafiori, Dimarco; Jorginho, Barella; Frattesi, Pellegrini, Chiesa; Scamacca
We say: Spain 2-1 Italy
Now meeting for the fifth straight Euros, these nations have been familiar foes in the Nations League too, and Spain's run of success over the Azzurri could continue.
A more diverse attacking approach paid dividends against Croatia, while Italy's defence remains a little dubious, so it may be La Roja celebrating safe passage to the last 16.