Both teams have dropped down from the Champions League qualifiers after suffering defeats on aggregate to Ludogorets and Dinamo Zagreb respectively last week.
Match preview
Shamrock Rovers missed the chance to progress to the third round of Champions League Qualifying after losing 4-2 on aggregate against Ludogorets.
The Hoops claimed a 2-1 second-leg win at home to the Bulgarian outfit, with Aaron Greene and Aidomo Emakhu both on the scoresheet, but their 3-0 first-leg defeat in Razgrad proved costly.
Stephen Bradley's side have since secured a comfortable 4-0 away victory over Bangor GG in the first round of the FAI Cup last Friday, with Emakhu again among the scorers along with Rory Gaffney, Sean Hoare and Daniel Cleary.
Shamrock, who are currently seven points clear at the top of the League of Ireland Premier Division with 12 games remaining, head into Thursday's tie unbeaten in each of their last 26 home matches across all competitions, with their last defeat at Tallaght Stadium dating back to August last year when they lost a Europa Conference League qualifier to Flora.
The last time the Hoops competed in the Europa League group stage was back in the 2011-12 campaign when they came up against Tottenham Hotspur, Rubin Kazan and PAOK.
Like Shamrock, North Macedonian outfit Shkupi were also defeated in the second round of Champions League Qualifying as they suffered a 3-2 aggregate defeat to Dinamo Zagreb.
Despite claiming a respectable 2-2 draw away from home in the first leg, the Pigeons were condemned to a slender 1-0 second-leg defeat last Wednesday, with North Macedonia international Arijan Ademi scoring the only goal of the game for the Croatian side two minutes after half time.
Shkupi, who were founded in 2012, won their first-ever top-flight title last season, winning 23 of their 33 matches and finishing 12 points clear of their nearest challengers.
Goce Sedloski's men will now be looking to gain an advantage in the first leg of their tie with Shamrock on Thursday, as they bid to qualify for the group stages of a major European competition for the first time in their history.
Shamrock Rovers form (all competitions):
Shkupi form (all competitions):
Team News
After making nine changes to his starting lineup for the game against Bangor GG, Shamrock boss Bradley is expected to recall a number of his key players and name a strong side on Thursday.
Strikers Greene and Graham Burke are set to lead the line, while midfielder Richie Towell and wing-backs Ronan Finn and Andy Lyons are also among those expected to start.
As for Skhupi, Sedloski will likely name a similar starting lineup to the one which narrowly lost to Dinamo Zagreb last week.
Last season's top scorer Sunday Adetunji, who netted 20 times in 28 league games, could be joined in attack by wingers Walid Hamidi and Renaldo Cephas, while playmaker Freddy Alvarez is set to line up in midfield alongside Queven and Faustin Senghor.
Shamrock Rovers possible starting lineup:
Mannus; Gannon, Grace, Hoare; Finn, McCann, O'Neill, Towell, Lyons; Greene, Burke
Shkupi possible starting lineup:
Naumovski; Brdarovski, Margvelashvili, Abdulla, Sheji; Queven, Senghor, Alvarez; Hamidi, Adetunji, Cephas
We say: Shamrock Rovers 1-1 Shkupi
With little to separate these two sides, a tight affair could be on the cards on Thursday, although Shamrock will fancy their chances of success considering their impressive unbeaten home record.