Third-placed Spurs are playing their home matches at Wembley as their new stadium is under construction.
"It's a massive game," Antonio added. "Even if it wasn't at Wembley, it would be a massive game...
"Especially after they beat us at home, we need to go there and beat them at their home. We've got to steady our minds, go there and perform for the fans."
Antonio last played at the national stadium in 2010 when he scored for former club Southampton in their 4-1 victory over Carlisle United in the EFL Trophy final.
"It's Wembley. As much as they are playing home games there all season, it's Wembley so it's exciting for any team that goes there," the 27-year-old told the club's website (www.whufc.com).
"There are going to be loads of players who have not had the opportunity to play there, who will now get the opportunity to play there. People are going to turn up and want to perform there because it is a historic ground.
"Scoring a goal at the historic Wembley Stadium was just unbelievable... I'd love to do it again on Wednesday night!"
West Ham will return to league action when they travel to bottom side Crystal Palace on Saturday.
(Reporting by Aditi Prakash in Bengaluru; editing by Sudipto Ganguly)
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