The Lilywhites stunned their opponents with the manner of their victory when the sides faced off three weeks ago, earning a comfortable 3-0 win through second-half goals from Son Heung-min, Jan Vertonghen and Fernando Llorente.
Following an impressive first half to the campaign for Dortmund, the wheels appear to have fallen off as they have ceded ground to Bayern Munich in the Bundesliga, exited the DFB-Pokal with defeat to Werder Bremen and are now on the brink of dropping out of the Champions League.
Twelve wins from 14 matches has since become one win in seven in all competitions for Lucien Favre's side, leading to a season that promised so much now becoming one to possibly forget.
Dortmund are still top of the Bundesliga, but the huge gap they had previously opened up on Bayern has now been completely closed and they lead by goal difference alone. Friday's 2-1 loss to Augsburg, coupled with the reigning champions' 5-1 win at Borussia Monchengladbach the following day, means that BVB are no longer favourites to win their first title in seven years.
To make matters worse for Favre, his side now require a miracle of sorts if they are to keep their European campaign alive. Many predicted a tight last-16 tie, but Dortmund collapsed in the second half against Spurs and only a three-goal win in the return match will prevent them from exiting the competition.
The German side conceded more goals in the first leg against Tottenham than they did in the entire group stage earlier this season (two), when topping Group A ahead of Atletico Madrid with 13 points from their six matches.
Having lost one out of their previous 14 Champions League knockout games, it is now 10 defeats in 13 such fixtures for Dortmund, who have been knocked out at the quarter-final stage twice and the round of 16 once since reaching the final in 2013.
A big part of Dortmund's problem in the first leg was the lack of quality on show from their attacking players - strange to say after conceding three times at the other end - as Mario Gotze, Jadon Sancho and Christian Pulisic only had one shot combined at Wembley Stadium.
Improvement is required at both ends of the field if Favre's charges are to pull off a major upset and make it through, though in all seven previous cases that a side has lost the first leg of a Champions League knockout match 3-0, they have unsurprisingly failed to overcome the odds on each occasion.
Recent form in Champions League: WWLDWL
Recent form (all competitions): LDLDWL
Like their opponents, Tottenham's campaign has also been derailed in the space of a five short weeks. Spurs exited both domestic cup competitions in the space of three days at the end of January, and a return of one point from nine in the Premier League has ended their outside title hopes.
After losing back-to-back matches against Burnley and Chelsea, Tottenham needed a response in Saturday's dramatic North London derby with Arsenal. In the end a 1-1 draw flattered Mauricio Pochettino's side somewhat, as they were given a lucky escape on home soil.
Rather than looking up at top two sides Manchester City and Liverpool, who are 10 and nine points better off respectively, Spurs are now looking over their shoulder at the chasing pack. Third place is still theirs to lose, but if this poor run of form continues then slipping out of the top four entirely should not be ruled out.
For now, though, Tottenham can turn focus back to the Champions League and a likely quarter-final tie. First comes this trip to North Rhine-Westphalia, which on the face of it seems a formality - avoid a 3-0 defeat and Spurs will be into the last eight.
Not since 2010-11 have the North London outfit made it that far in UEFA's showpiece competition, having exited at this same stage 12 months ago with a slightly cruel 4-3 aggregate defeat to a Juventus side that simply outsmarted them.
Lessons have been learned from that tie, and Pochettino now wants his side to keep their campaign alive by completing the job against Dortmund and setting themselves up for a last-eight clash with another European superpower.
Tottenham's victory in the first leg was their joint-biggest margin of victory in the Champions League, winning by three clear goals for the fifth time in the competition.
Spurs have also scored in each of their last 17 Champions League games - their longest run in the competition - and they have only ever lost one game in the Champions League (out of 31 played) by more than two clear goals, against Real Madrid at the Bernabeu in April 2011 (0-4).
Their domestic campaign may have fallen apart of late, but Tottenham remain on course for a memorable season on the European stage.
Recent form in Champions League: LDWWDW
Recent form (all competitions): WWWLLD
Spurs welcomed Vertonghen back from a hip injury against Arsenal, but they were without Harry Winks for that match because of a similar problem.
Pochettino is likely to stick with his three-man backline, with Ben Davies in contention to take over from Vertonghen at left wing-back from the first leg, and Victor Wanyama is also in contention to start his second game in the space of three days after proving his fitness.
In terms of the hosts, skipper Marco Reus played no part in the first leg because of an issue to his thigh, but he was back in action against Augsburg last week, lasting a little over an hour.
Pulisic was also absent for that match but he is back in training, three weeks on from injuring his thigh against Spurs, and the Chelsea-bound attacker has been given a chance of making the starting lineup on Tuesday.
Raphael Guerreiro has scored four of Borussia Dortmund's last five goals in the Champions League.
Borussia Dortmund possible starting lineup:
Burki; Guerreiro, Diallo, Akanji, Hakimi; Witsel, Delaney; Sancho, Reus, Pulisic; Alcacer
Tottenham Hotspur possible starting lineup:
Lloris; Alderweireld, Sanchez, Vertonghen; Aurier, Sissoko, Wanyama, Davies; Eriksen; Son, Kane
Head To Head
Tottenham have won all three of their previous encounters with Dortmund in the Champions league, twice in last season's group stages and also in the reverse fixture last month.
The match at the Westfalenstadion finished 2-1 to the Lilywhites thanks to goals from Harry Kane and Son after Pierre-Emerick Aubameyang, now plying his trade for rivals Arsenal, had opened the scoring for BVB.
Spurs and Dortmund also faced off in the 2015-16 Europa League, with the latter winning 3-0 in the first leg of their last-16 tie before completing the job with a 2-1 victory at White Hart Lane.
We say: Borussia Dortmund 2-1 Tottenham Hotspur (2-4 on aggregate)
Both teams have struggled for form in recent weeks, but it is Tottenham who have a stranglehold on this tie. Victory in the first leg made it four wins in a row for Pochettino's side, though they have since lost two and drawn one. It will take an almighty effort from Dortmund to turn this one around, however, even if they do come out on top on the night.
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