United welcome the Saints to St. James' Park (8pm kick-off) for the second leg of their Carabao Cup semi-final - with a trip to Wembley awaiting the winners.
The Magpies carry a one-goal lead into the game thanks to Joelinton's strike at St Mary's last week but Howe has warned his side that the tie is far from over.
Ahead of what is set to be a raucous night under the lights on Tyneside, Newcastle's head coach sat down with the media at United's Benton training centre to preview what has been billed as his club's biggest encounter in decades.
Here are some of the key topics up for discussion on Monday morning:
On what he learned from the first leg on the South Coast, and the prospect of Tuesday's decider...
"It was a tight game. I think first half we probably shaded it, second half definitely for a spell of 20-25 minutes they shaded it and we were indebted to Nick (Pope) to make a couple of really big saves in the game.
"Overall I was pleased with our performance but we know Southampton are a strong team. They've added players in the window as well, I think they've got a big squad, a talented squad and a new manager, a very talented manager. Certainly from our perspective - and I've drilled this into the players this week - this game is by no means over. This tie is not over. It's very much in the balance. We're going to need a top performance and we're going to need the crowd with us from minute one to the end, and hopefully we can get through."
On the importance of having a sold-out home crowd behind him and his side...
"Hopefully we can get the crowd into the game early, thrive off their positivity and it can elevate us in terms of our performance levels.
"You never know how football match is going to go - it can be unpredictable, and there can be twists and turns in cup ties. From our side, we need to be resilient and be able to take whichever way the game turns and be strong in that moment. I'm sure the crowd will, but support us in that moment, because this is going to be a really difficult game for us."
On his selection dilemmas and the possible involvement of Alexander Isak, who has impressed off the bench in recent weeks...
"Certainly we've got decisions to make in a few positions, and that's great from my perspective, that we have competition building. The guys who have come onto the pitch in recent weeks have excelled and done really well and that always gives you decisions to make. We're looking at and analysing training as well, and the majority of the squad has trained well this week, so I'll have a big call to make as I do most games."
On the signing of Anthony Gordon over the weekend...
"He'll give us a lot. I think he's a young player with huge attributes, huge potential to have a big impact on our season. He's a very quick, dynamic player, (he's) versatile - he can play off both sides. The best is yet to come from him, but he can add something different for us and I'm delighted to get him.
"I think we're getting someone who is fiercely determined, ambitious, and I think he's got a nice balance between confidence and knowing there's areas to improve in his game. I've got no doubts about his character - we've done a lot of research with every signing, and there's always a risk with every signing, because you never quite know until you work with a player how that dynamic will be.
"But we've tracked him for a long, long time, since the early days at Everton and the loan spell he had, so I think we know the player and I'm really pleased he's now part of our team."
