The Major League Soccer regular season returns in full with Miami, who travel to the New York Red Bulls, faced with the tough task of climbing from bottom place in the Eastern Conference and into the play-off positions.
Prior to the break for the Leagues Cup - and Messi's arrival along with Sergio Busquets and Jordi Alba - Miami were winless in 11 games in MLS with the worst record in the entire league.
In most leagues in the world, a team in that position would be focused purely on avoiding relegation from the top flight.
But MLS has no relegation and instead has a play-off system that could yet offer a way for the new-look Miami, under Argentine coach Gerardo 'Tata' Martino, to compete for the title.
The top nine finishers in each conference earn a spot in the play-offs with the top seven going into the first round, best of three series of games.
The eighth and ninth-placed teams play each other in a single elimination 'wild card' match to get into the first round.
Miami are currently 14 points behind ninth place with 12 games left and so have little room for error in the remainder of the season.
But the form they have shown since the arrival of Messi and his two former Barcelona teammates, unbeaten in eight games, albeit winning three of their knockout ties via penalties, suggests such a play-off push is not out of the question.
It will be a long slog to turn Inter's MLS season around and adding to the difficulty of the task, Martino admitted after Wednesday's shoot-out win over Cincinnati in the US Open Cup, that his star man was amongst those feeling the pace of their recent exertions.
"Both Leo and many other players are reaching an important physical limit and from today we will evaluate how we approach the next three matches," he said.
"The fatigue is overcome with all the enthusiasm ... I hope the team in the future could play better, but it's very difficult to do that when you almost can't rest," he added.
It would not be a shock then, for one or more of Messi, Busquets and Alba, to start on the bench at Red Bull Arena on Saturday with Martino retaining the option to throw them on in the second half.
The Red Bulls are in 11th place in the East, 11 points ahead of Miami, and have their own hopes of clambering into the post-season.
Saturday's games see Eastern Conference leaders Cincinnati host 2021 champions New York City, while in the West, top-placed St.Louis City, enjoying a dream first season in the league, are at Orlando City.
Defending champions Los Angeles FC travel to North Carolina to face Charlotte FC.
