The reigning Western Conference champions Spurs (15-3) feature 10 international players and the Timberwolves (9-10) have seven on their squad amounting to a record total for an NBA contest.
"It's great to have a match-up where we can showcase the most international players," Philippe Moggio, the NBA's vice president for Latin America, told Reuters.
"It demonstrates the flavour of internationalism within the NBA, particularly for Latin America," he added, noting Minnesota's Ricky Rubio of Spain and Jose Juan Barrea of Puerto Rico along with San Antonio's Manu Ginobili of Argentina and Brazil's Tiago Splitter.
Moggio has called Mexico "a priority market" for the NBA, which is staging its 21st game there, the most for any country outside the United States and Canada.
Globalisation is a watchword for the leading professional basketball league, which next month shifts NBA action to London for a game between the Atlanta Hawks and Brooklyn Nets after a record spate of eight pre-season games staged overseas.
While international revenues represent a modest amount of the NBA's projected total of over $5 billion, it is a fast-growing segment.
More than 30 per cent of league merchandising sales come from outside the United States and more than half of NBA.com's 9.6 billion page views and 5.6 billion video streams come from outside North America, the league says.
Barea, who joined the T-Wolves two season ago after winning an NBA ring with the Dallas Mavericks over LeBron James and the Miami Heat, represented the NBA in Mexico City last year at the finals of a national school basketball tournament.
"They love the NBA and basketball is growing there," Barea told the Star Tribune of Minneapolis. "It's a big place: a lot of traffic, a lot of people, but a lot of the fans of the NBA. It's going to be crazy."
In the United States, the Hispanic community is becoming a major supporter of the league, according to Saskia Sorrosa, NBA Vice President, Marketing.
Sorrosa said market research six years ago led the NBA to alter their online approach to better reach the US-Hispanic audience and that had helped spark a dramatic gain.
"We found that the bulk of our Hispanic fans were bicultural, bilingual," Sorrosa told Reuters. "We had been targeting this audience with Spanish language play-by-play, everything in Spanish.
"They like to see our games in English but read the stories in Spanish."
They renamed the modified NBA Hispanic site "ene-be-a", as the acronym sounds when pronounced by Spanish speakers, and the enhanced site triggered what Sorrosa called "gigantic growth" across media and merchandise.
Fifty-four per cent of those attending Miami Heat games last year were Hispanic, as well as 53 per cent of the crowd that came to see the Spurs and 41 per cent in Houston.
Sorrosa said Hispanic-Americans made up 17 per cent of the NBA's fan base overall, comprising 26 per cent of 6-to-11 year-olds, and 20 per cent of the 12-17 age bracket.
"There's definitely a higher concentration in the younger generation of the Hispanics in the country," she added. "As the generations get older, a much larger percentage of our fan base will be Hispanics, continuing to drive our business."
Wednesday's game marks just the second regular season contest held in Mexico City following a 1997 tilt between Dallas and Houston.
Moggio blamed the long wait for another regular season south of the US border to facilities.
"For us to be able to take a team outside of their home market and make it a home game for them, we need to ensure that it's going to feel like playing in an elite arena like in the US," said Moggio.
"Here in Mexico there wasn't an arena up to NBA standards until last year when the Mexico City arena came on line. It's a great arena where we played our first preseason game last year.
"Certainly it's something that we contemplate," he said about increasing the number of regular season NBA games held outside the US and Canada.
Moggio said another boost for NBA Latin America is the 2016 Rio Olympics, which moved the NBA to hold a preseason game this year in Rio for the first time.
"After we announced our game in Rio, we launched a Facebook page a little less than a year ago and got 240,000 followers," he said. "That's helping us keep the momentum in the sport."