Oscar Tabarez's side will play their final warm-up game ahead of the FIFA World Cup with doubts lingering over whether star striker Luis Suarez will regain full fitness in time for their opening match against Costa Rica.
The Liverpool man had minor knee surgery last month after sustaining a partial lateral meniscus injury.
While Uruguay are hopeful Suarez will be ready to shine in Brazil, a home game against Slovenia in Montevideo presents a golden opportunity for the likes of Stuani and Hernandez to bolster their claims for a starting berth.
Stuani scored the winner against Northern Ireland on Saturday and Lugano feels both the Espanyol striker and Palermo's Hernandez are capable of impressing.
However, although Uruguay also have Edinson Cavani and Diego Forlan at their disposal, Lugano has acknowledged the importance of Suarez being available at the World Cup.
"Suarez is irreplaceable," he is quoted as saying by The Daily Mail.
"He's our best player, the one who makes the difference. His injury weakens us but if he doesn't make it, Uruguay aren't going to play with 10 men. Someone will come in and play for him.
"Stuani is in great shape. He's sharp and very hungry, and Abel Hernandez is ready to break through."
Suarez is set to rejoin Uruguay's squad this week as he seeks to prove his fitness.
"We'll not decide the XI until the day before the (Costa Rica) game," Tabarez added, when questioned on Suarez's chances of playing in Uruguay's World Cup opener.
"Luis will join the squad this week and, depending on how his knee responds, we'll see how soon we can count on him to start a game."
Slovenia missed out on qualification for the World Cup and face two friendlies against high-calibre South American opposition before beginning their bid to reach the 2016 European Championships.
Wednesday's clash with Uruguay will be followed by a match against Argentina on Saturday.
Uruguay and Slovenia have met just once before - with the former running out 2-0 winners in a friendly that took place in February 2001.
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