Messi curled in a superb strike in the 62nd minute at Miami's Nu Stadium to fire Inter into a 2-1 lead, but Nashville grabbed a share of the points after striker Sam Surridge bundled in an injury-time equaliser.
The 39-year-old Messi has now scored a remarkable 17 goals in 14 games against Nashville in all competitions since joining Miami in 2023.
And Messi could have even improved his goals record against Nashville in Saturday's game between the first-placed and second-placed sides in the Eastern Conference.
Messi saw a shot crash off the underside of the bar in the 50th minute and also saw a shot cannon off the post in the 78th minute. A late Messi effort was also headed clear by Nashville defender Jeisson Palacios before Surridge's leveler.
The result leaves Inter nine points adrift of Nashville in the race for top seeding with nine regular season games remaining.
Earlier, Nashville had got off to a dream start when English striker Surridge sprang the offside trap before burying a low shot into the bottom corner in the fourth minute.
But Miami drew level midway through the half and again Messi was involved. The World Cup-winner's wicked in-swinging corner found the head of Nashville defender Reed Baker-Whiting, who glanced in an own goal.
It looked as if Messi had grabbed the winner midway through the second half when he combined with former Argentina international teammate Rodrigo De Paul on the edge of the area before curling a shot beyond the dive of Brian Schwake.
But Miami's failure to extend their lead proved costly as Surridge scored from close range in injury time to steal a point.