Meanwhile, the hosts are entering Europe's top tier competition at this stage after winning their 23rd Croatian top-flight crown in the 2021-22 season.
Match preview
Holding a seven-point buffer over closest challengers Hadjuk Split, Dinamo Zagreb were crowned champions of Croatia for the fifth season running last term - beating the eventual runners-up 3-1 on the final day of the campaign.
A mid-season managerial change saw 68-year-old Ante Cacic take the reins from Zeljko Kopic, and he led his side to an unbeaten and goal-laden pre-season period before their domestic campaign also began in ideal fashion with a Super Cup win on penalties against Split.
Dinamo Zagreb also kicked off their new league campaign with a hard-fought 3-2 success over local rivals Lokomotiva Zagreb on Friday, with the champions only just scraping the win through Luka Menalo's injury-time header after playing the final 12 minutes with an extra man.
The reigning Croatian champions have previously participated in the group stage of the Champions League on seven occasions and reached the last-32 of the Europa League last term before bowing out to six-time winners Sevilla, so there is no debate as to where the European nous lies ahead of the first leg.
Furthermore, not since December 2021 have Dinamo Zagreb suffered a home defeat in any competition, and even Sevilla lost 1-0 on Croatian turf in Europe last term, so not many bets will be placed on Shkupi upsetting the apple cart this week.
While Dinamo Zagreb enjoyed a free pass into the second round of qualifying, Shkupi were forced to do it the hard way against Lincoln Red Imps in round one and very nearly let their Gibraltar-based counterparts overturn a 3-0 first-leg advantage.
Juanfri and 40-year-old Lee Casciaro netted in the second leg to reduce the deficit to 3-2, but Lincoln Red Imps were ultimately unable to find the back of the net for a third time as Shkupi advanced to the second round by the skin of their teeth.
The Macedonian champions - who won the First Football League for the first time in the 2021-22 season, 10 years after their formation - are competing at the top level of European football for the first time this season after suffering three straight first-round eliminations in Europa League qualifying between 2019 and 2021.
Goce Sedloski's side also fell at the second hurdle in Europa Conference League qualifying to Santa Clara last season, and they will at least have another go at Europa League qualifying if Dinamo Zagreb prove too strong over the course of 180 minutes this month.
Dinamo Zagreb form (all competitions):
Shkupi Champions League form:
Team News
Dinamo Zagreb left-back Petar Bockaj was taken off with just 24 minutes gone in the recent win over Lokomotiva Zagreb, and on the other side, Stefan Ristovski was also forced off injured in the second half.
Cacic may therefore have to call upon Sadegh Moharrami and Daniel Stefulj to fill the voids on the flanks this week, while Menalo has also put his name in the hat for a start over Dario Spikic.
Josip Drmic came off the bench to net twice in league action on Friday and will feel hard done by if he does not start this one, either in place of or alongside Bruno Petkovic.
As for Shkupi, midfielder Aleks Zlatkov was a half-time withdrawal in the 2-0 loss to Lincoln Red Imps last week, although his substitution was believed to be a tactical decision.
Nevertheless, the 20-year-old is now at risk of ceding his place to the more experienced Kristijan Ackovski, and Sedloski may be tempted to deploy another centre-back in the hopes of avoiding a first-leg thumping.
Melos Bajrami would be drafted back into the side if Sedloski opts for a defensive setup, while one-cap Nigeria international Sunday Adetunji will lead the line after registering 20 goals and six assists in 28 games last season.
Dinamo Zagreb possible starting lineup:
Livakovic; Moharrami, Theophile-Catherine, Sutalo, Stefulj; Ademi, Ljubicic; Menalo, Ivanusec, Orsic; Drmic
Shkupi possible starting lineup:
Naumovski; Brdarovski, Senghor, Abdulla, Sheji; Queven, Ackovski, Alvarez; Cephas, Adetunji, Danfa
We say: Dinamo Zagreb 3-0 Shkupi
The magnitude of the occasion very nearly got the better of Shkupi in their second leg with Lincoln Red Imps, but they can at least take confidence from firing three past their counterparts in the first leg.