Spurs started the Premier League season with three victories, but successive defeats against Watford and Liverpool have dampened the mood around the club.
Inter have been unimpressive in Serie A, winning just one of their opening four games.
The two sides have met on four previous occasions, with each recording tow victories.
Their most recent meeting came in the last 16 of this competition back in 2012/13.
Spurs won 3-0 at home before Inter scored three at home in the second leg to send the game to extra-time.
Both sides scored in the additional period to send Spurs through on away goals.
Inter are priced at 17/10, with Spurs on offer at 7/4 and the draw available at 9/4.
Confirmed starting line-ups:
— Inter (@Inter) September 18, 2018
#THFC: Vorm, Aurier, Sanchez, Vertonghen, Davies, Dier, Dembele, Eriksen, Lamela, Son, Kane (C).
— Tottenham Hotspur (@SpursOfficial) September 18, 2018