The long-time couple first got together almost 20 years ago in the Channel 4 soap, but Luke's alcoholism and Mandy's infidelity with Darren Osbourne will force her to end things for good.
Viewers will watch next week as Mandy tearfully confesses to her year-long affair with Darren to his partner Nancy, before immediately telling Luke that their relationship is over.
Speaking exclusively to The Sun Online's Soap Bubble, actress Sarah Jayne Dunn, 36, revealed that there's finally no going back for the pair.
"Mandy and Luke were amazing, childhood sweethearts who found each other again. They were supposed to be together, but certainly not no," she says.
"There's love, but it's more friendship than passion now for those two."
The actress added: "She does love Luke and that's the reason they've stayed together, and that's the reason she's stayed by his side for so long."
And now, with Luke set to exit the soap for the short term while actor Gary Lucy takes part in the Full Monty stage tour, that gives Mandy the perfect opportunity to move on guilt free.
She says: "It does mean that Luke will be out of the equation, but it still doesn't fix things.
"What's great about this storyline is that it's just going to continue to run, despite the fact the affair comes out and it's now dealing with the grown up stuff and the real life thing of Mandy and Darren being selfish.
"[Mandy's been so busy] she hasn't seen what's going on with everyone else – that her son's being abused, that her husband's still struggling, all of these things are happening and she's overlooked it because she's gone for what she wanted."
And the confession has been a long time coming, with the affair beginning almost a year ago.
Sarah revealed: "It was great, we were all waiting for it to come out obviously, we knew from the beginning that it was going to be a long running thing.
"I think that's great because it makes it realistic. It means the timescales are true to life.
"We were always excited for this reveal as well, I think we were all like 'Oh my God it's going to happen soon, I can feel it'.
"It's bubbling, the tension's there, it's going to blow. It was brilliant to film – it's been great working with these guys. It's been a really good storyline for us all.
"But no-one expected Mandy to just admit to the affair without any prompting, especially after all the scheming Mandy has done to keep it a secret.
"It all comes to a head and the confession [happens] between Mandy and Nancy and then Nancy goes mental, as you would expect, and then there's all the repercussions about how everyone else finds out.
"Then it's how everyone else reacts.
"It's been a good storyline, in that it's all of these friends who have been friends for a very long time, that have got a lot of history between the four of them as couples, and they've got children.
"So the big thing about it is the repercussions – not just the reveal. It's everything that happens afterwards.
"Obviously the reveal is a big moment and everything hits the fan but it's then how the characters deal with it afterwards."
And for Mandy, she has to confess because she just wants to be with Darren and can't hide it anymore.
Sarah added: "There's a reason they've been having this affair and it's not stopped and that it's carried on.
"That reason is that they really love each other and they do want to be together but it's not as easy as that and there's a lot of people involved, and a lot of people they would hurt if the truth came out, hence why they'd been keeping it a secret.
"But they've got to a point where they decided that actually they wanted to be together and they were just biding their time and waiting for the right moment for this to happen.
"It's been boiling, and its been bubbling, they both knew that at some point they would reveal what's going on and say they wanted to be together.
"Because of that it just comes out, it's one of those things that they're so desperate to be together and neither of them are happy in their own relationships so it's just a case of it all just gets too much and finally it's this is the truth of it all."
But if Mandy and Darren weren't to work out then Sarah is very clear that Mandy should stop going back to old boyfriends to find happiness.
She said: "She'd be better off starting from scratch because this revisiting people is clearly not working for her.
"If it doesn't work with Tony, and it doesn't work with Luke, and then if it doesn't work with Darren then I really think she should probably be on her own and have some time to herself.
"She just jumps from relationship to relationship which isn't great. She's always chasing the happily ever after and bless her she doesn't ever find out.
"She definitely shouldn't go back to Warren."
But before all of that she's got to survive Nancy's revenge after she turns to an unlikely source for help – Sienna Blake.
On the prospect of being kidnapped and being locked up, something called a Sienna Special on the show for the sheer amount of times she's done it, Sarah laughed: "Oh yeah, totally [locked up with] Rick Astley.
"Quite possibly that could be the the next storyline.
"Sienna's character is just so unhinged, so getting her involved…
"You do worry what's going to be in the next script that you pick up but I think it's what makes the show great.
"We've got some really heavy hard-hitting storylines, and we've got some real fun, and then we've got the soapy stuff, it's all there and people love it.
"And it's soap, isn't it? So you can get away with loads of stuff that in real life you'd go 'WHAT?!'."
- Hollyoaks airs weeknights on Channel 4 at 6.30pm with a first look episode on E4 at 7pm
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