As a result of the draw in Nyon, goalkeeper Hugo Lloris will return to the Stade Gerland for the first time since moving to London for 10million euros this summer.
"It's a tough draw and this is the first time in nine years they've not been in the Champions League," Eales told Sky Sports News.
"There are a lot of tough teams in the draw. We can ask Hugo the way to go and I think he will be excited about the chance to go back to his old team and play there."
Eales believes Villas-Boas has what it takes to lead Spurs to the European title after he engineered a win for former club Porto during a treble-winning first season in charge, which saw his side also lift the Portuguese Cup and win the Primeira Liga.
"He's got the pedigree so hopefully he can do what he did with Porto two years ago and we can go all the way to (the final in) Amsterdam," he said.
"We want to be playing in European competition. We don't see why we can't have a successful Europa League campaign and do well in the league."
Inter Milan will come up against Tottenham should the Barclays Premier League side get past Lyon, with Cluj standing in the Italians' way.
Nerazzurri representative and former Portugal winger Luis Figo is nervous about facing the Romanian side, who dropped out of the Champions League.
He told inter.it: "Cluj won the title in their country. They came close to advancing in the Champions League, so we'll have to do our best.
"We'll have to face them with all our strength and how things go will also depend on how we are in February."
European champions Chelsea travel to Sparta Prague after becoming the first Champions League holders to exit the competition at the group stage, with Liverpool taking on Russian giants Zenit St Petersburg over two legs.
Liverpool manager Brendan Rodgers told reporters: "It is a good draw for us. We have had the experience of Russia (playing against Anzhi Makhachkala in the group stages) and it was important for us to win the group which means the second leg will be at home.
"We have a lot of games and a lot of thinking to do before then. It's exciting but the most important thing is we're in the draw for the next round. It's against another team who have invested an awful lot of money to win things and do well.
"But there are a lot of games to go before that and obviously nearer the time our focus will turn more towards it."
Newcastle boss Alan Pardew admitted the club's tie against Ukraine's Metalist Kharkiv will be a trip into the dark.
Asked what he knew about their opponents, Pardew said: "Not much, really. I do know it's a long journey, I've had a look at that, and they won their group, so it's a tough agenda for us."
Elsewhere, Lazio face Borussia Monchengladbach, with Biancocelesti head coach Vladimir Petkovic saying: "Last year they came close to a Champions League place and they have been doing very well lately.
"They're not an easy opponent but it's not impossible."
Monchengladbach director of sport Max Eberl said: "This is an incredibly attractive draw for us. The games against Lazio are going to be great challenges."
In the other games, Champions League dropouts BATE Borisov face Fenerbahce, while Levante take on Olympiacos and Dynamo Kiev take on Bordeaux.
Ajax host Steaua Bucharest while Stuttgart host Genk and Bayer Leverkusen play Benfica.
Swiss champions Basle play Dnipro, Russia's Anzhi play Hannover and Napoli take on Viktoria Plzen.
Europa League last-32 draw
BATE Borisov vs Fenerbahce
Inter Milan vs Cluj
Levante vs Olympiacos
Zenit St Petersburg vs Liverpool
Dynamo Kiev vs Bordeaux
Bayer Leverkusen vs Benfica
Newcastle vs Metalist
Stuttgart vs Genk
Atletico Madrid vs Rubin Kazan
Ajax vs Steaua Bucuresti
Basel vs Dnipro
Anji Makhachkala vs Hannover
Sparta Prague vs Chelsea
Borussia Monchengladbach vs Lazio
Tottenham vs Lyon
Napoli vs Victora Plzen
Europa League last-16 draw
Napoli/Plzen vs BATE/Fenerbahce
Leverkusen/Benfica vs Dynamo Kiev/Bordeaux
Anji/Hannover vs Newcastle/Metalist
Stuttgart/Genk vs Monchengladbach/Lazio
Tottenham/Lyon vs Inter/Cluj
Levante/Olympiakos vs Atletico/Rubin
Basel/Dnipro vs Zenit/Liverpool
Ajax/Steaua vs Sparta Prague/Chelsea