A faltering campaign has left Argentina fifth in the standings with three games remaining, just outside the top four spots which guarantee automatic entry to next year's finals in Russia.
It would still take a dramatic sequence of results for the unthinkable -- a World Cup without Argentina and Messi -- to become reality.
Even if Jorge Sampaoli's side fail to lock up automatic qualification, and finish fifth, they would still be favourites to qualify via a two-leg playoff against a team from Oceania, almost certain to be New Zealand.
An uninspiring 0-0 draw with Uruguay in Montevideo on Thursday left Argentina level on 23 points with fourth-placed Chile, who lead on goal difference.
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Sampaoli is expected to persist with the bulk of the team who started against Uruguay, with Messi leading a potent front three that features Paulo Dybala and Mauro Icardi. Javier Mascherano could return for the suspended Gabriel Mercado, while Ever Banega may replace Guido Pizarro.
"We have to be more aggressive in the last third and get more people in the area," he said following the Uruguay stalemate.
"We have to ensure that the team wins. We have to win so that Argentina can be at the World Cup in Russia."
- Chile turmoil -
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Despite the nervyness of Argentina's campaign, their fans can console themselves by the thought that Chile have hardly been any more convincing.
The Chileans face Bolivia again tomorrow in La Paz, an awkward tie at altitude even if their opponents, who are already eliminated, have little to play for.
Chile's faltering qualification campaign suffered a fresh jolt last week with an abject 3-0 home defeat to Paraguay in Santiago.
The Chileans, who clinched back-to-back Copa America titles in 2015 and 2016, have been beset by turmoil, with Arsenal's Alexis Sanchez struggling to find his best form and captain Arturo Vidal raging at his media critics.
"I'm sure all the critics are happy now," Vidal wrote. "But don't worry, each time I'm closer to leaving."
It was left to Chile coach Juan Antonio Pizzi to strike a defiant note as his team head to La Paz, insisting that his squad would rediscover the attacking vigour that won them their Copa America crowns.
"We are convinced that we will find the identity that made us champions of South America twice," Pizzi said.
Third-placed Uruguay meanwhile face a testing away trip to seventh-placed Paraguay, who could thrust themselves back into the qualification reckoning with a win. Paraguay are on 21 points, just two behind Argentina and Chile.
Peru (21 points) could also enhance their chances if they manage to score a third consecutive win in their assignment in Quito against eighth-placed Ecuador (20 points).