Both men were last in action at the Australian Open, where each lost in the third round, Wawrinka letting a two-set lead slip against Marton Fucsovics while Khachanov fell to Matteo Berrettini in three tiebreakers.
This is the fourth career meeting between the two men with Wawrinka leading the head-to-head 2-1. The match is scheduled third on Center Court not before 2:30pm Rotterdam time with the winner facing British qualifier Cameron Norrie in the second round.
There will be a ton of shot-making on display from both players with Wawrinka relying on one of the best one-handed backhands in tennis while Khachanov will look to his forehand to do most of his damage.
Control of the baseline will be key as both men will want to dictate from there. The Russian will look to set things up with his big serve and forehand while the Swiss will try to bully Khachanov with that heavy backhand. Wawrinka's forehand let him down against Fucsovics and that is his weaker side.
The fourth seed will also need to serve well and engage in long rallies against Khachanov, who can overhit at times if he gets impatient. The Russian does move well for someone who stands 6'6".
Both players will want to put the disappointment of their last match in Melbourne behind them and pick up a quality win to begin this ATP World Tour 500 event.
The court is playing slow, which may slightly benefit Wawrinka and he has also already played a match here in doubles, so he is used to the speed.
The stadium is also brand-new, which means Khachanov may need time to adjust, but if he can he has an excellent chance to emerge victorious. In what will be a long affair, the three-time major champion should triumph in what should be the best match of the tournament so far.
Prediction: Stan Wawrinka in three sets