The only team to beat Argentina in the nine matches so far, Venezuela have grown into a confident side who believe they could also defeat the group leaders on their home patch.
"Venezuela have progressed and everything they have achieved was earned because this team is quite different from that playing the qualifiers years ago," Argentina midfielder Javier Mascherano told reporters.
Victory would give Argentina a six-point lead in the qualifying table, if Colombia fail to beat Bolivia, but Venezuela are in fighting mood after their 1-0 win in Puerto de la Cruz in October 2011.
"It's motivating to beat Argentina or get a good result against them," said coach Cesar Farias. "Nowadays it's not crazy to think of taking points at the Monumental.
"This Argentina is much better than (the team) that went to Puerto de la Cruz but Venezuela are also a more mature national team," he told reporters.
Lionel Messi's team will want a good result at the Monumental ahead of their daunting trip to high-altitude La Paz four days later when they will be out to avenge a 6-1 pasting by Bolivia when Diego Maradona took Argentina there in 2009.
Argentina lead the nine-nation South American group with 20 points, three more than second-placed Ecuador who face Paraguay at home on Tuesday.
Messi, who has had his baby son Thiago's name tattooed on his left leg, shares top place in the scorers' list in the qualifiers with team mate Gonzalo Higuain and Uruguay's Luis Suarez, with seven goals.
Sergio Aguero, who has three goals, will be missing for Argentina because of injury and winger Angel Di Maria is suspended. Ezequiel Lavezzi and Walter Montillo are likely to take their places.
Colombia, being moulded into an exciting attacking force by former Argentina coach Jose Pekerman, are third, four points off the pace, going into their home match with Bolivia in the Caribbean city of Barranquilla.
Striker Radamel Falcao has notched up five goals and Porto's James Rodriguez has been equally influential from midfield.
Venezuela, in the last of the four qualifying berths for next year's finals in Brazil, have 12 points, ahead of Uruguay on goal difference.
The team in fifth place after the final round of group matches in October will meet an Asian side in a playoff for one more berth, a position Uruguay found themselves in four years ago before their remarkable run to the semi-finals in South Africa.
Chile, also on 12 points in sixth, are under new coach Jorge Sampaoli, who replaced fellow Argentine Claudio Borghi in December after three defeats in a row.
The Chileans travel up the Pacific coast to Lima to face arch-rivals Peru, who have a fight on their hands if they want to reach the finals for the first time since 1982.
Sampaoli will be without Juventus midfielder Arturo Vidal, who is serving out the remainder of a three-match suspension in the two March qualifiers, but Chile welcome back Gary "Pitbull" Medel, who can put some bite back into their midfield.
Copa America holders Uruguay need a victory over bottom team Paraguay in Montevideo to get back on track after picking up only one of the last 12 points and conceding 12 goals in the process.