In a four-team group, avoiding defeat in the opening game is crucial, so it is a vital encounter for both of these nations.
Ever since Mexico first entered the Copa America in 1993, they have been a competitive force.
That year they finished as runners-up when they lost out to a brace from Argentine striker Gabriel Batistuta in the final and since then, only once - in 2011 - have they failed to progress beyond the group stages.
They also impressed during last year's World Cup, where they collected seven points from games against Cameroon, Croatia and hosts Brazil, before they were beaten in controversial circumstances by Louis van Gaal's Netherlands in the first knockout round.
However, this edition of the Copa America is likely to be a major test for Miguel Herrera and his charges. With the Gold Cup coming up next month, Herrera, who has made himself a popular figure with his eccentric style on the touchline, has been forced to prioritise.
The 47-year-old appears to have put his eggs in the Gold Cup basket, so he has decided to rest the likes of Javier Hernandez, Andres Guardado, Hector Herrera, Diego Reyes and the Dos Santos brothers, none of whom will feature in Chile. Consequently, aside from Rafael Marquez, it is a largely inexperienced squad that will compete at the Copa.
Preparation for the tournament has been mixed as they beat Guatemala and drew with Peru, before recently being defeated 2-0 by Brazil.
Recent form: WLWLLL
Recent form (all competitions): WWLWDL
El Verde have reached the final of this tournament twice, one of which they won in 1963, while in 1997 they were defeated 3-1 by Brazil, who had Ronaldo among the goalscorers.
It is worth noting, though, that on both of those occasions, they were the host nation.
Indeed, the majority of Bolivia's victories are achieved at home, where they tend to benefit from playing in La Paz, which is 3,600 metres above sea level. It's a notoriously difficult environment to play in, where the air is a lot thinner, making it difficult to breathe for those that are not accustomed to it.
Their struggles away from home are there for all to see when it comes to other Copa America tournaments. They are without a win in the last five instalments of the competition. Also, in the last World Cup qualifying campaign, they won just two of their 16 matches.
Mauricio Soria's men have played just one warm-up fixture, but they will probably wish that they had avoided it. Argentina, who are 14-time Copa America winners, ran out 5-0 winners in San Juan on Sunday thanks in part to a hat-trick from Manchester City striker Sergio Aguero.
Soria is the third coach to have taken charge of the Bolivians in their last four matches.
Recent form: LLLDWL
Recent form (all competitions): DLDDLL
He may be 36 and a veteran of 126 caps, but captain Marquez is expected to take his place in the heart of Mexico's three-man defence.
Further up the pitch, in the absence of Hernandez, Atletico Madrid frontman Raul Jimenez will spearhead the attack as he looks to add to his six goals at senior international level.
As for Bolivia, their attack should feature Marcelo Martins, who despite having scored 12 goals for El Verde, has not found the net for his country in over two years.
Mexico possible starting lineup:
Corona; Dominguez, Marquez, Ayala; Corral, Osuna, Fabian, Aldrete; Herrera, Jesus, Jimenez
Bolivia possible starting lineup:
Quinonez; Rodriguez, Eguino, Zenteno, Morales; Bejarano, Gamarra; Escobar, Lizio, Smedberg-Dalence; Moreno
Head To Head
Of the 11 meetings between these two nations, Bolivia have won just once and tasted defeat on nine occasions.
Nevertheless, they can perhaps take some heart from the fact that their sole win over the Mexicans was achieved in the Copa America 18 years ago when Erwin Sanchez, Ramiro Castillo and Jaime Moreno scored in a 3-1 triumph.
On a more worrying note, in the previous four editions of this fixture, Mexico have scored 13 goals, with Bolivia finding the net just once during that time.
We say: Mexico 2-1 Bolivia
It may be a largely untested Mexico side as far as international tournaments are concerned, but they still have some quality players in their ranks. Meanwhile, Bolivia have been in quite rotten form and providing that Mexico perform to their best level, they should have enough to edge this game.