Semak was handed control of first-team affairs at Zenit last week following the departure of Luciano Spalletti and will oversee his first UEFA Champions League match on Wednesday at Signal Iduna Park.
However, it could well be his last for some time with Andre Villas-Boas strongly tipped to be announced as Spalletti's long-term successor and Dortmund strong favourites to progress to the quarter-finals.
Things could be much worse for Zenit, given that Dortmund - last seasons's Champions League runners-up - moved two goals ahead inside six minutes in the first leg of their last 16 tie, which took place in Russia last month.
However, Jurgen Klopp's side will have to suffer an unlikely collapse on home turf if Zenit are to progress.
Dortmund have won eight of their last nine Champions League home games, with a 1-0 defeat to Arsenal in this season's group stage the only setback.
Zenit, meanwhile, head into Wednesday's game having triumphed in just one of their last seven Russian Premier League matches.
Spalletti's exit followed a goalless draw with Tom Tomsk and Zenit then suffered a 1-0 defeat to CSKA Moscow at the weekend in Semak's first game at the helm.
Belgian defender Nicolas Lombaerts says he and his team-mates must take responsibility for the club's poor form.
"If the coach is fired, the players should take a look at themselves. In the end, if he was fired, then we're one of the main causes," Lombaerts told the club's official website.
"But unfortunately that's the life of a head coach, and we have to move on. We're playing for Zenit, so we have to do everything to get back on top."
While Dortmund slipped up with defeat at the weekend, they are still a point ahead of third-placed Schalke in the Bundesliga - with the two sides due to meet next Tuesday.
They also remain in contention for the DFB-Pokal and history suggests they will progress to the quarter-finals of the Champions League as well.
In the 12 UEFA competition ties where Dortmund have won the first leg away from home, they have triumphed on aggregate 11 times.
Striker Robert Lewandowski has underlined the team's eagerness to bounce back after the loss to Monchengladbach.
"Of course we can play better. In the end, a draw would have been fair. Now we need to check off the defeat quickly and focus on Zenit St. Petersburg on Wednesday," he told Dortmund's official website.
Klopp could be without Marco Reus, who has missed Dortmund's last three games with a muscle problem, while Zenit's Aleksandr Ryazantsev, a January signing from Rubin Kazan, is not registered for the UEFA Champions League.
