These two countries with a combined population of 13.5 million have always been overachievers on the global scene - the last decade under Tabarez has seen two-time former winners Uruguay reach one World Cup semi-final and win one Copa America, while Portugal triumphed at Euro 2016.
Uruguay looks a tough side to crack with Atletico Madrid centre-back partnership proving quite a handful to the teams that have faced it.
Uruguay midfielder Matias Vecino said his team would need to be careful not to give Ronaldo too many free-kick chances.
Portugal won one and drew two of their three group matches this summer.
Ronaldo is known to get visibly frustrated when he fails to score or make an impact in the game while Suarez's antics are known to all.
Ahead of the highly-anticipated match, Portugal coach Fernando Santos signalled a subtle warning to his talisman to keep a check on his nerves during the match. "That means he has a very strong relationship with his players".
Uruguay star striker Luis Suarez is on the opposite end of the famed Clasico rivalry with Ronaldo's Real Madrid, but the Barcelona man told reporters that has nothing to do with Saturday's World Cup clash.
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"It's the team that has to play, if Ronaldo plays alone we're going to lose".
Another World Cup quarterfinal spot is on the line this Saturday when Uruguay takes on Portugal in the round of 16 in Russian Federation.
"They are a typical South American side", said Santos.
All five of Uruguay's goals at the 2018 World Cup have been scored from set-pieces (three from corners, one from a direct free-kick and one from an indirect free-kick). "Not just Godin. We will have to work collectively in order to try and limit the effect that he can have".
In Godin and Jose Gimenez, Uruguay have one of the most priceless commodities in global football - a centre-back pairing which plays together week in and week out for Atletico Madrid.
The teams will meet at 2 p.m. ET on Saturday in a World Cup Round of 16 game.
If he plays, Portugal's Cristiano Ronaldo (37) will equal Bastian Schweinsteiger (38) as the player with the most appearances at World Cups and European Championships. - Penalty shootouts excluded, Portugal has lost only one of its last 17 games at major tournaments (W8 D8), a 4-0 defeat against Germany at Brazil 2014. "We're there to win".