The young Magpies - who have played the majority of their home fixtures at Whitley Park - head into the Premier League 2 clash on the back of four consecutive wins in all competitions, with Ben Dawson's side securing their play-off place in Division Two after a 3-2 comeback win at Stoke City.
United sit in third place on 37 points, two adrift of league leaders Southampton, and the 20-year-old shot stopper is hopeful of replicating positive memories experienced at St. James' Park this season in their bid for promotion.
He told nufc.co.uk: "I'm really looking forward to the game. Any chance to play at St. James' Park is a massive opportunity, especially against a team such as Man United.
"It should benefit the squad in playing at St. James' rather than Whitley Park because everybody gets a buzz when they play at a stadium, especially Newcastle's home ground.
"One of the stand out games was against Macclesfield in the Checkatrade Trophy. It was one of the biggest games in our season and to save the penalty, which helped to send us through to the next round, was a great feeling.
"When we were playing at Stoke (at the bet365 Stadium), the squad were talking about the big effect of playing at home compared to other stadiums. Being at home and knowing this is your stadium and you belong there is massive. With the stands hanging over you, it does give you a big lift."
Newcastle enjoyed an impressive 4-1 victory at Manchester United back in November, with Elias Sørensen bagging a brace at Leigh Sports Village along with strikes from Cal Roberts and Yannick Touré.
Although their play-off spot is already confirmed, Harker understands the importance of their final two league contests, beginning with the final home game of the league season against the Red Devils, which will be streamed live on NUFC TV.
He added: "When we look at the top of the table, we are looking to achieve promotion in our final two games. We want to finish as high as we can and although it's possible to win the league, it's not in our hands at the moment so we are looking at taking it one game at a time.
"The two games are very important if we are to finish well. If we get into the play-offs, we know finishing strongly in the division can get us a home draw which would be massive for the team as it would be another opportunity to play at St. James'.
"We want to finish on a high and playing at St. James' Park gives us the biggest chance to do that. It would be a great way to finish our home campaign by beating Man United.
"We beat them 4-1 away from home and, although we knew we were capable of winning, we didn't expect it to go so well. Hopefully, we can take what we learnt in the away leg and apply it to the game on Monday."