While the Bees were enjoying their mid-season break, Spurs lost at home to Manchester City last time out and will now seek their first league win of 2024.
Match preview
Having beaten their opponents on all five previous occasions they had met at Tottenham Hotspur Stadium, Spurs were ready to relinquish that streak and settle for an FA Cup replay last week, but the clubs' fourth-round tie ultimately went the way of Man City.
Nathan Ake's much-disputed late goal decided matters in the holders' favour, leaving Ange Postecoglou's men with only the Premier League to concentrate on between now and the end of the season.
A 16-year silverware drought goes on, so Spurs now turn their attention to staying in touch with the top four - and holding off challengers from behind, such as Manchester United, who held them to a 2-2 draw earlier this month.
On that occasion, Tottenham trailed twice but bounced back each time with goals from Richarlison and Rodrigo Bentancur, and their last league win now dates back to New Year's Eve.
Although City shut them out last Friday, Spurs have scored in each of their last 33 top-flight matches, which represents the club's longest streak throughout their whole league history - and the fourth-best run by any side in the Premier League era.
They have also lost just one of their last nine league games against Brentford ahead of this week's home contest, though that defeat did come in the equivalent fixture last season.
Having been beaten in their first Premier League meeting with Spurs in late 2021, Brentford have since gone undefeated through the last four - including that 3-1 victory at Tottenham Hotspur Stadium in May.
Like their midweek hosts, the Bees were recently knocked out of the FA Cup, with their brief journey coming to an end in a replay against Wolverhampton Wanderers after the sides had drawn 1-1 in London first time around.
Then, to much fanfare, talisman Ivan Toney returned from his long ban to captain the team that took on fellow strugglers Nottingham Forest last time out in the league, when victory ended a five-game losing streak.
After six losses from seven overall, Brentford finally got back to winning ways with help from Toney's opening goal, for which the England striker employed a dose of dark arts, and further strikes from Ben Mee and Neal Maupay during the second half.
They have, though, lost all of their last four Premier League away games, and after embarking on a 14-match unbeaten run in London derbies they have since lost their last two - going down 1-0 to Arsenal and 3-1 at Crystal Palace.
With his side still perched perilously close to the relegation zone, Bees boss Thomas Frank will therefore seek to end both streaks by toppling Spurs on Wednesday.
Tottenham Hotspur Premier League form:
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Tottenham Hotspur form (all competitions):
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Brentford Premier League form:
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Brentford form (all competitions):
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Team News
Ange Postecoglou is missing three important players again, as Spurs skipper Son Heung-min remains on Asian Cup duty with South Korea, while midfield duo Pape Sarr and Yves Bissouma are still away at the Africa Cup of Nations.
Alejo Veliz (knee), Manor Solomon (knee) and Giovani Lo Celso (thigh) are sidelined too, but Tottenham fans welcomed the return of James Maddison as a substitute last week, after his absence with an ankle injury since November. Ben Davies was also back on the bench.
Although Maddison will soon be pushing to start, Postecoglou may name a similar starting XI on Wednesday evening, with in-form Richarlison leading the line up front. The latter has scored six goals in his last six Premier League appearances - as many as in the previous 47 - and eight of his 10 goal involvements this season have come from his last seven home matches.
Meanwhile, Brentford's attack will be spearheaded by Ivan Toney, who quickly found the net on his return to action against Nottingham Forest last time out.
Recent loan signing Sergio Reguilon will not be eligible to face his parent club, while fellow full-backs Rico Henry (knee) and Aaron Hickey (thigh) are among several players out injured.
Bryan Mbeumo (ankle), Kevin Schade (groin) and Christian Norgaard (ankle) remain unavailable too; Yoane Wissa, Saman Ghoddos and Frank Onyeka are all on international duty.
Though the Bees have reportedly beaten Tottenham to a £25m deal for Club Brugge winger Antonio Nusa, the Norway international will spend the rest of this season on loan at his former club.
Tottenham Hotspur possible starting lineup:
Vicario; Porro, Romero, Van de Ven, Udogie; Hojbjerg, Bentancur; Johnson, Kulusevski, Werner; Richarlison
Brentford possible starting lineup:
Flekken; Collins, Pinnock, Mee; Roerslev, Janelt, Jensen, Damsgaard, Lewis-Potter; Toney, Maupay