Messi scored his first and only hat-trick for Argentina in a 3-1 friendly win away to Switzerland in February so pasting over cracks in coach Alejandro Sabella's defence.
Right-back Pablo Zabaleta pointed to the imbalance of an Argentina side with a world class group of forwards but a rearguard short of choice in full backs and quality in central defenders.
"To have Leo [Messi], Pipa [Gonzalo Higuain] and Kun [Sergio Aguero] gives you maximum security," Zabaleta said.
"Up front we have great power, the strongest point in this national team and let's hope they get chances and put them away," he told reporters after a practice.
Uruguay, ranked third by FIFA, will not take Venezuela lightly having paid a price when they were beaten 3-0 at home in 2004 by the region's one-time whipping boys.
"Let's hope it isn't as tough this time. We're on the right track. In any case all the teams are very even... we hope not to end up like the last times, suffering and doing sums," striker Luis Suarez told reporters.
COACH'S DEBUT
Messi and Aguero were partly responsible for their compatriot's appointment, their goals in Argentina's 2-1 away win over Colombia in their last qualifier in November earning coach Leonel Alvarez the sack.
Injuries are plaguing coach Sergio Markarian's plans again with strikers Claudio Pizarro out and Jeferson Farfan doubtful.
"In the face of this adversity, I think the Peru team can overcome them. At the Copa America important players were also injured and in the end we had a good cup," striker Paolo Guerrero told reporters.
