Santos, inspired to the South American club title by Pele in 1962 and 1963, are favourites after last week's 0-0 draw in the first leg at the Centenario in Montevideo where Neymar was below his best and Ganso absent after a thigh injury.
Ganso, having recovered, is deemed fully fit to turn out in the second leg at the Pacaembu in Sao Paulo, reuniting the gifted duo whose exciting link play has made them the biggest sensation in Brazilian football.
Since Ganso suffered his injury in May only two months after returning from knee surgery that put him out of action for 199 days, the 21-year-old has been groomed for this final - at first for both legs until Santos decided to aim for the second.
"Ganso has worked hard at his conditioning and is very close to the ideal (fitness). I think he can play the whole match," Santos doctor Rodrigo Zogaib told reporters.
"As he is a very technical player, he won't have much difficulty with the rhythm (of the game). He knows how to pace himself."
Ganso and the 19-year-old Neymar are at the heart of Brazil coach Mano Menezes's attacking game for next month's Copa America in Argentina.
Winning the Libertadores Cup would confirm that despite their youth, the pair are ready to handle that responsibility.
Uruguayan teams are noted for their exploits in Brazil and Penarol coach Diego Aguirre says the tie is still wide open.
"They're a great team, they have national team players, we could face a similar Santos (to the Centenario), perhaps more daring," Aguirre told Reuters in Montevideo.
"The chances are they will beat you but the fact is that the series is open," said Aguirre, whose side upset holders Internacional 2-1 in Brazil on their way to a record 10th final.
Penarol have striker Juan Manuel Olivera, their top scorer in the competition with five goals, nursing a shoulder injury he suffered in the first leg but expect him to be fit for the match as they seek their sixth title.
Since 2000, in seven finals in which Brazilian teams have faced foreign sides with the second leg played in Brazil, they have only prevailed once - when Internacional won the title last year.
Santos lost to Argentina's Boca Juniors in their third final in 2003.
