Consecutive 3-0 wins over Turkey and Switzerland mean Italy is already sure of a place in the Round of 16 and will be guaranteed to top Group A if it avoids defeat in Rome on Monday (AEST).
Wales, meanwhile, drew with Switzerland before producing a fine 2-0 win over Turkey that means it needs only a point to progress to the knockout stages.
Italy is undeniably favourite to win the game, having secured 10 consecutive victories without conceding a goal. Should it avoid defeat, it will match its all-time record of 30 games in a row unbeaten, which was set between November 1935 and July 1939.
Mancini expects Wales to present a very difficult challenge, though, much like the Potters did during his days as Manchester City manager: in eight Premier League games, Mancini managed four wins and four draws against Stoke.
"Stoke had a very tough style of play, they were a very tough nut to crack," Mancini said ahead of facing Wales.
"It will be a very difficult match from a physical perspective because they are a powerful side like Stoke, but they are also very technical.
"Wales have players like [Joe] Allen, [Gareth] Bale and [Daniel] James. They have got some quality and skilful players."
Mancini will rotate his side for the game at Stadio Olimpico, with Marco Verratti in line for his first performance of the tournament after recovering from a knee problem.
"Tomorrow ... will be our third game and we would have rotated regardless, even if this was a must-win fixture," he said. "A third game in the space of 10 days with 30-degree heat, you need fresh legs out there.
"Marco needs to play. Until today, after so many days of training, he is fine."