In a section also featuring 2021 finalists England and Italy, the hosts will be keen to record maximum points as they begin their bid to qualify for a second straight European finals.
Match preview
While twenty teams will earn their place at next year's finals through a top-two finish in qualifying, only another three will join those nations and the hosts via the playoffs.
Given the difficulty of their draw, North Macedonia may already be contemplating the latter route to UEFA's international showpiece, though they have beaten both Germany and Italy in recent years as their star began to rise.
Following the Balkan nation's tournament debut at Euro 2020 - and their subsequent victory over the Germans in Duisburg - they came within 90 minutes of reaching last year's World Cup; after sensationally knocking Italy out in Palermo, Blagoja Milevski's men fell to Portugal at the final hurdle.
However, North Macedonia have won just two of their last nine competitive games following a disappointing Nations League campaign in League C, and they signed off for 2022 with a miserable 3-1 home loss to Azerbaijan.
Having only beaten lowly Gibraltar since upsetting Italy, they have been struggling for goals and are five games without a win coming into their first fixture of Euros qualifying.
The Lynxes have, though, won five and drawn one of six previous meetings with Malta at senior level, so at least history is on their side when they seek to start 2023 in better style.
Ranked 167th in the world by FIFA, Malta have unsurprisingly never made it to a major finals before, and their goal in the qualifiers will again be to develop new talent and take a handful of points.
Last year, the Falcons finished behind Estonia in their Nations League group - both defeats to the eventual winners coming by the same 2-1 scoreline - and only ahead of San Marino, but there have been some signs of improvement for the Mediterranean minnows.
Autumn friendlies against Israel and Greece brought a 2-1 success over the former and a creditable 2-2 draw with the latter, though they concluded their calendar for 2022 with a reverse to the Republic of Ireland in Ta'Qali.
As Group C favourites Italy and England are likely to tussle with Ukraine to secure automatic qualification for the finals, Malta may now see their two contests with North Macedonia as the best chance to post a positive result under new management.
Set to host the Italians on Sunday, Michele Marcolini's men could be in for a rough ride over the coming months, so will at least hope to avoid defeat in Skopje.
North Macedonia form (all competitions):
W
L
L
L
D
L
Malta form (all competitions):
L
W
L
L
D
L
Team News
With AEL midfielder Davor Zdravkovski being the only uncapped member of North Macedonia's squad for both Thursday's qualifier and a friendly against the Faroe Islands at the weekend, the hosts should field a familiar side.
Todor Todorovski is sidelined by suspension, though, following his dismissal against Bulgaria in the Nations League last September.
Stole Dimitrievski starts in goal, Enis Bardhi and Napoli's Eljif Elmas will feature in midfield, while Saudi Arabia-based Aleksandar Trajkovski should join Milan Ristovski up front. Since the international retirement of all-time record holder Goran Pandev, Trajkovski is the Lynxes' leading active scorer on 20 goals.
Meanwhile, Italy-born coach Michele Marcolini has included new-boys Luke Tabone and Yannick Yankam in his first Malta squad.
Tabone, of Gzira United, steps in for Birkirkara defender Enrico Pepe, who was unable to recover from injury in time for selection, while Valletta's Triston Caruana also misses out.
Having made a big impact as captain of surprise Europa League quarter-finalists Union Saint-Gilloise this season, Teddy Teuma will play a creative role in the visitors' midfield.
North Macedonia possible starting lineup:
Dimitrievski; Zajkov, Ristevski, Velkovski, Alioski; Ashkovski, Bardhi, Ademi, Elmas; Trajkovski, Ristovski
Malta possible starting lineup:
Bonello; Z. Muscat, S. Borg, Apap; J. Mbong, Guillaumier, Paiber, Camenzuli; Teuma, Jones; Satariano