Nico Barella and Romelu Lukaku were on the scoresheet for the Italian giants in Portugal, with Simone Inzaghi's side taking control of the tie by recording a 2-0 win.
Inter will now be aiming to finish the job in front of their own fans, with Benfica having a mountain to climb when it comes to progressing to the final four of the competition.
Inter will enter the match off the back of a 1-0 defeat to Monza in Serie A at the weekend, while Benfica suffered a 1-0 loss to Chaves, which made it three straight defeats in all competitions for the Eagles.
Here, Sports Mole takes a look at the head-to-head record between the two sides ahead of the second leg of their last-eight contest on Wednesday night.
Last week's first leg was just the fourth time that Inter and Benfica had faced off, with the Italian side, as mentioned, running out 2-0 winners in Portugal courtesy of goals from Barella and Lukaku.
Their first ever meeting took place in the final of the European Cup in May 1965, with Inter recording a 1-0 victory in Milan courtesy of a first-half effort from Jair.
Inter have only won the European Cup once since then, lifting the trophy in 2010, which proved to be their third success in the competition.
Benfica, on the other hand, have won the European Cup on two previous occasions, with their victories coming in 1961 and 1962, beating Barcelona and Real Madrid in back-to-back years.
The two sides also locked horns in the last-16 stage of the UEFA Cup during the 2003-04 campaign.
The first leg in Portugal finished in a goalless draw, suggesting that the second leg would also be a tight and cagey affair, but it was actually a seven-goal thriller at San Siro.
Nuno Gomes sent Benfica ahead in the 36th minute, but Inter led 3-1 just past the hour courtesy of goals from Obafemi Martins, Alvaro Recoba and Christian Vieri.
Benfica were back in the match in the 67th minute when Gomes struck his second of the match, but Martins then scored another in the 70th minute.
Tiago Mendes sent up a grandstand finish by making it 4-3 in the 76th minute, but the visitors could not find a fourth, with Inter progressing to the quarter-finals, where they were beaten by Marseille.
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