West Ham will face record Europa League winners Sevilla in the last 16 of the competition, while Borussia Dortmund's conquerors Rangers are rewarded with a tie against Red Star Belgrade.
The Hammers sailed through the group stages of the competition, winning four from six of their pool matches and are now set to face Julen Lopetegui's men, firstly away from home.
It will be a big test of just how far David Moyes' men have come over the past few years, particularly with their Premier League form slightly faltering of late.
Rangers meanwhile, arguably took out the biggest threat in Borussia Dortmund and will now face, on paper at least, a more winnable tie against Red Star Belgrade.
Moyes has done a wonderful job in his second stint as West Ham manager and getting his side to the knockout stages of the Europa League is perhaps the high watermark.
They have gone from being a team of underachievers to one of the most well-balanced teams in England and now have a further opportunity to shine on the European stage.
However, with Dortmund out, it is fair to say they have probably been handed the toughest draw possible.
Not only have Sevilla won this competition a record six times - last achieved in 2020 when beating Inter Milan in the final - they are also performing remarkably well domestically.
Ex Spain boss Lopetegui has got them sat second in the division and they are the only realistic candidates to stop Real Madrid reclaiming the La Liga title.
Sevilla are 17/20 to win the first leg with West Ham 16/5, and a draw priced at 12/5.
Rangers' result against Borussia Dortmund was quite remarkable and it will have given manager Giovani Van Bronckhorst a real shot in the arm, particularly with the Gers slightly losing grip of the Scottish Premiership defence.
Even though Dortmund were without star forward Erling Haaland, it was always going to be a big ask for Rangers but they managed to overcome the German giants 6-4 on aggregate.
They're up against former European Cup winners Red Star Belgrade who finished top of Group F, but only managed to win three of their group games.
Rangers will therefore view them as beatable and they are priced at 8/13 to win the first leg with Belgrade 19/4, and a draw 13/5.
Elsewhere, Barcelona face Galatasaray in a match between two fallen giants of European football, though the former are steadily improving under Xavi.
They were very good in beating Napoli 4-2 in the second leg of the play off round and now face a Galatasaray side who are 13th in the Duper Lig and way off European qualification.
There is an interesting battle between Atalanta and Bayer Leverkusen with both sides faring in Italy and Germany respectively while 2011 winners Porto are in action against Lyon, with the whole draw looking very competitive.
Leicester's domestic form has been awful in 2022 with the Foxes failing to win a game so the thrashing of Randers will have provided much-needed relief.
Their next test in the Conference League will come in the form of Rennes, who got through to this round by virtue of their unbeaten group stage.
However, like the Foxes, their recent form has not been so good, losing six of their last 10 Ligue 1 games. Leicester are currently 1/1 to win the first leg with Rennes 11/4, and a draw 12/5.