Spurs will enter the match off the back of a morale-boosting 5-2 win over Southampton in the Premier League, while Orient shared the points with Mansfield Town in their last league encounter.
Orient's 2019-20 campaign might have ended in March, but Ross Embleton's side have been busy at the start of this season, already taking to the field on five occasions for competitive fixtures.
The O's have beaten Forest Green Rovers and Plymouth Argyle in the first two rounds of the EFL Cup to advance to this stage, while they also overcame Brighton & Hove Albion's Under-21 side 3-2 in the EFL Trophy earlier this month.
Orient started their League Two season with a 1-0 win at Oldham Athletic on September 12, meanwhile, before, as mentioned, sharing the points with Mansfield on Saturday afternoon.
Tuesday will actually bring the first meeting between these two sides since January 2001, when Tottenham ran out 1-0 winners in the third round of the FA Cup.
Spurs would not have been feeling fantastic about themselves after losing 1-0 to Everton on the opening weekend of the new Premier League season, while they only just overcame Lokomotiv Plovdiv in the Europa League on Thursday night courtesy of two goals in the latter stages.
Deals for Real Madrid duo Gareth Bale and Sergio Reguilon were secured ahead of Sunday's Premier League clash with Southampton, though, and Jose Mourinho's side emphatically overcame the Saints, with Son Heung-min scoring four times in a 5-2 win at St Mary's.
Tottenham's fixture list is incredible as they face a trip to North Macedonia to take on Shkendija in the third qualifying round of the Europa League on Thursday night, before hosting Newcastle United in the Premier League on Sunday afternoon.
The games are coming thick and fast for Spurs, and Orient will certainly be looking to take advantage of the fact that the top-flight club have bigger fish to fry than the League Cup.
Leyton Orient EFL Cup form: WW
Leyton Orient form (all competitions): WWWWD
Tottenham Hotspur form (all competitions): LWW
Orient boss Embleton is expected to shuffle his pack from the side that faced Mansfield in the league on Saturday as the hosts have an important game away to Walsall on September 26.
The XI is expected to have a similar look to the one that started against Plymouth in the previous round, meaning that Lee Angol could be handed the striking role in a 4-2-3-1 formation despite Danny Johnson's excellent form.
Tottenham will be without the services of Japhet Tanganga due to a thigh problem, while new signing Bale is out until October with a knee injury.
Mourinho is expected to make wholesale changes from the side that faced Southampton, and there could be a debut for former England number one Joe Hart between the sticks.
New signing Reguilon could also be involved in the squad despite concerns over his fitness.
Leyton Orient possible starting lineup:
Vigouroux; Thomas, Turley, Coulson, Widdowson; McAnuff, Wright; Dennis, Maguire-Drew, Sotiriou; Angol
Tottenham Hotspur possible starting lineup:
Hart; Aurier, Alderweireld, Foyth, Cirkin; Gedson, Sissoko; Lamela, Alli, Sessegnon; Bergwijn
We say: Leyton Orient 1-3 Tottenham Hotspur
Orient will be full of confidence after an excellent start to the season, but there will be a big jump in quality on Tuesday night, even though Mourinho is expected to make wholesale changes. Spurs will not view the EFL Cup as a priority this season but should ease into the fourth round of the competition here.