The Silkmen, who are the only remaining Northern Premier League side left in the competition, booked their place in the last eight on Saturday after overcoming National League South side Hampton & Richmond 2-0.
Quickfire second half goals from Lewis Fensome and Sam Heathcote saw Alex Bruce's side advance at the expense of higher-league opposition for the fourth successive round.
Macclesfield have also knocked out National League North duo Alfreton Town and Curzon Ashton, before thrashing National League strugglers Dorking Wanderers in the fourth round.
Discussing the chances of his players causing another cup upset ahead of the draw, Silkmen boss Bruce said: "They've shown, especially in the cup against teams from higher leagues, what they're capable of.
"It's about doing that on a consistent basis, and if we can do that, it could be a really good season for everyone involved with the club.
"Two games from Wembley, I've said that to the lads. With the group that we've got, there's no reason why we can't go and achieve what we want to achieve."
Standing in their way of a semi-final spot are Bishop's Stortford, who are currently bottom of the National League North, and Coalville, sat 13th in the Southern Central League.
The pair saw their initial fifth round tie postponed over the weekend so will attempt to lock horns again on Tuesday night.
Quarter-final ties will take place on Saturday 9 March, with winners receiving £7,500 and losers £2,000.
FA Trophy fifth round ties involving NPL clubs:
Macclesfield v Bishop's Stortford or Coalville Town