The Major League Soccer All-Star side have downed some high-profile European sides in recent years.
For the 2017 edition of the clash, an MLS All-Star side that includes Kaka, David Villa, Sebastian Giovinco, Michael Bradley and captain Bastian Schweinsteiger will take on La Liga and UEFA Champions League winners Real Madrid at Chicago's Soldier Field on Wednesday.
Read on for viewing and scheduling details, along with a preview of the clash and predictions.
Date: Wednesday, August 2
Time: 9 p.m. ET/8 p.m. local/2 a.m. BST (Thursday)
TV Info: FS1 (U.S.), Sky Sports Football (UK)
Real have not enjoyed the best pre-season so far. They lost 3-2 to Spanish rivals Barcelona in Florida on Saturday after a 4-1 drubbing at the hands of Manchester City in California.
Los Blancos managed a 1-1 draw with Manchester United in their first International Champions Cup game of the summer but lost eventually on penalties.
They return to Europe after the MLS All-Star Game for another clash with the Red Devils in the UEFA Super Cup, and manager Zinedine Zidane will likely be eager his side head into that on August 8 clash on the back of a win.
However, it will be a tough ask given the quality of the MLS outfit. Along with the major overseas names like former Real player Kaka, former Barca forward Villa and former Germany skipper Schweinsteiger, and current United States captain Bradley heads a strong core of U.S. internationals.
Veteran goalkeeper Tim Howard is in the squad alongside Jozy Altidore, Dax McCarty and DaMarcus Beasley.
Meanwhile, Real will be without star man Cristiano Ronaldo but can still call upon the phenomenal likes of Gareth Bale, Karim Benzema, Isco, Luka Modric and Marcelo.
Real have more quality in their ranks and, given their recent form in La Liga and the Champions League, should easily beat the All-Stars on Wednesday if they play to their best.
But the Spanish giants are still in preparation mode. They are missing arguably their best player and are not firing on all cylinders.
Conversely, the MLS stars are in midseason form and will be raring to go, eager to claim such a huge scalp as Real.
Villa and Giovinco are both in flying form in front of goal, the former having netted six times for New York City FC in his last seven MLS outings, the latter scoring four in four for Toronto.
With the huge incentive of downing the best team in Europe to spur them on, the MLS All-Star side could well pull off a shock on Wednesday and down Real in Chicago.
Predicted Score: MLS All-Stars 3-2 Real Madrid