With a spot in Brazil already assured, the hosts will look to gather some more momentum against the already-eliminated visitors
Alejandro Sabella has a wealth of talent at his disposal for the South American qualification fixture - which will see his top-placed side entertain struggling Peru in Buenos Aires - even though three of his regulars have been forced to withdraw.
Captain Messi and his Barcelona team-mate Javier Mascherano are both out of the clash at El Monumental with hamstring injuries, while Napoli striker Higuain is sidelined with a calf problem.
However, with the likes of Manchester City's Sergio Aguero, Real Madrid's Angel Di Maria and Paris Saint-Germain's Ezequiel Lavezzi all available, Sabella will be confident of maintaining his side's unbeaten home record in qualifying.
Meanwhile, Inter striker Mauro Icardi could make his international debut for Argentina after the 20-year-old was rewarded for his solid start to the new Serie A campaign with a first call-up.
Argentina lead the Conmebol table with 29 points from their 14 matches, with Colombia their only realistic challengers for top spot with 26 points with just two games remaining.
They secured their place at Brazil 2014 with a 5-2 destruction of Paraguay in their previous qualifier on September 11.
Two Messi penalties and strikes from Aguero, Di Maria and Maxi Rodriguez were enough to ensure the country will compete for their third World Cup crown next year.
However, Peru's hopes of reaching a first World Cup finals since 1982 were officially ended when they lost both of their September qualifiers against Uruguay and Venezuela.
Those results mean Sergio Markarian's charges have 14 points from as many games and can no longer reach fifth place, which would have earned them an intercontinental play-off with Jordan in November.
Peru entered qualification with high hopes after a third-place finish in the 2011 Copa America, but they were unable to continue that momentum and have collected just four wins throughout the campaign.