Cesar Farias' men sit sixth in the South American qualification section, just three points behind Uruguay, who currently occupy the all-important fifth spot that will earn a play-off against either Jordan or Uzbekistan.
Meanwhile, Peru travel to Puerto La Cruz just two points behind Venezuela, although their chances of finishing fifth took a severe blow when a Luis Suarez double condemned them to a 2-1 home defeat to Uruguay on Friday.
Sergio Markarian's side have now lost their last two qualifiers, but will be buoyed by the fact they came from behind to beat Venezuela 2-1 in the reverse qualifying fixture in Lima last September.
Jefferson Farfan netted twice on that occasion after Juan Arango's opener for Farias' team and the Schalke forward - along with Bayern Munich striker Claudio Pizarro - is again likely to be their main threat.
Venezuela go into the match in desperate need of a positive result to snap their sequence of four CONMEBOL qualification fixtures without a win.
They were beaten 3-0 by an in-form Chile in Santiago on Friday, and slumped to a 1-0 defeat to Uruguay in their previous home qualifier in June.
Jose Rondon is Venezuela's top scorer with four goals in qualifying so far, and Farias will again look to the Rubin Kazan forward for inspiration as he seeks to guide his country to their first ever World Cup finals.
Recent history favours Peru, though, as they have won three of the last four meetings between the countries.
However, Venezuela came out on top when they last hosted Peru in World Cup qualification in September 2009, when Nicolas Fedor struck twice in a 3-1 win.
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