Both nations boast proud football heritage and go into the last four Euros match in fine form through the 2021 tournament.
Italy saw off top-ranked team Belgium in their quarter final which extended the Azzurri's unbeaten run to 32 games in all competitions.
Semi final opponents Spain found the going tough in their quarter final, needing penalties to see off a spirited 10-man Switzerland side after it ended 1-1.
Spain, under coach Luis Enrique, are themselves unbeaten in 13 games and will go into the last four match with Roberto Mancini's Italian side full of confidence too.
It will be the first meeting between two of European football's historical powerhouses since the 2012 Euros final in what is built up to be one of the game's of the tournament.
Here's when Italy vs Spain is being played, kick off time, ticket information and TV coverage.
When is Italy vs Spain?
Italy and Spain will play each other in the semi final of Euro 2020 on Tuesday 6 July.
What time does Italy vs Spain kick off?
The kick off for Italy vs Spain is scheduled for 8pm (BST) on 6 July.
Where is Italy vs Spain being played?
Wembley Stadium will host the first semi final of Euro 2020 between Italy and Spain.
The same venue will be the setting for England vs Denmark 24 hours later and the final of the 2021 football tournament on Sunday 11 July.
Can I get Italy vs Spain tickets?
Tickets are currently on sale for both Euro 2020 semi finals between Italy vs Spain and England vs Denmark at Wembley Stadium.
Capacity limits on Wembley have been relaxed for the knockout rounds of the 2021 Euros despite delays to lockdown rules amid the Covid pandemic.
Both semi finals and the final of Euro 2020 will form part of the UK government's events research programme designed to bring large crowds back to live events.
These events are given special permission to increase the number of people through the gates if they comply with certain requirements such as showing proof of Covid vaccination or a negative Covid test result.
Wembley's capacity has been increased to 60,000 for the three Euro 2020 games.
Tournament organisers UEFA advise that all those interested in purchasing tickets will need to live in the UK, Ireland, Isle of Man, Guernsey or Jersey.
What TV channel is Italy vs Spain on?
The semi final match between Italy and Spain will be aired live on BBC One.
Can I live stream Italy vs Spain?
Alternatively, UK license fee holders can also live stream Italy vs Spain for free through the BBC's streaming platform iPlayer.
What are the odds on Italy vs Spain?
Italy are hot favourites with online bookies to extend their 32-game unbeaten run against Spain in the semi finals of Euro 2020.
Punters can get odds of 6/4 on Italy winning, with Spain 2/1 to reach the Euros final, according to comparison site oddschecker.com.
Italy vs Spain prediction
Italy to win 2-1.