It will be the first time the hosts have taken part in the Champions League group stage since the 2007-08 season. Dortmund, meanwhile, are set to compete for the fifth consecutive campaign.
After guiding Lazio to fourth place last campaign, finishing only five points behind champions Juventus in the end, it has been a more difficult start for Simone Inzaghi's side this time around.
Striker Ciro Immobile won the European Golden Shoe last season with an astonishing 36 league goals, which was the first time a player other than Lionel Messi, Cristiano Ronaldo or Luis Suarez had won the award since Diego Forlan did so in 2008-09.
However, the Italy international has only scored once this season and missed the defeat to Sampdoria having been sent off in the previous match against Inter Milan, so he will be more motivated than ever to get back to scoring ways with his former club heading to Rome.
The 30-year-old spent a season with Dortmund in the 2014-15 campaign, scoring only three league goals in 24 appearances as the German side plummeted to finish seventh in Jurgen Klopp's last season at the club.
It would be fair to say that neither individual has looked back since, though, with Klopp achieving great success at Liverpool and Immobile scoring an incredible 125 goals in his four full seasons so far at Lazio.
It has been a much smoother ride for Lucien Favre's Dortmund in the Bundesliga, with Saturday's excellent 1-0 win at Hoffenheim taking them up to third in the table with three wins and a loss after four matches.
Erling Braut Haaland and Marco Reus both came off the bench in the weekend's win, with Reus scoring the decisive winner in the 76th minute, which suggested Favre may have had an eye on this forthcoming Champions League fixture.
With Zenit St Petersburg and Club Brugge drawn alongside these two sides in Group F, BVB are in the relatively unusual position of being heavy favourites to win a favourable looking group.
Laying down a marker at the Stadio Olimpico, then, may be an important step on the path to living up to that billing and safely progressing to the knockout stages.
Lazio form (all competitions): WLDL
Borussia Dortmund Champions League form: WLWW
Borussia Dortmund form (all competitions): WWLLWW
Dortmund are without Marcel Schmelzer (ankle), Nico Schulz (calf) and Dan-Axel Zagadou (knee), with Thorgan Hazard and Lukasz Piszczek unlikely to shake off their recent knocks in time for the trip to Rome.
Reus and Haaland should come into the front three alongside Jadon Sancho, with Giovanni Reyna and Julian Brandt dropping to the bench. Young England prospect Jude Bellingham will be hoping to make his Champions League debut in midfield alongside the experienced Axel Witsel.
Lazio possible starting lineup:
Strakosha; Patric, Acerbi, Hoedt; Parolo, Leiva, Milinkovic-Savic, Alberto, Marusic; Immobile, Correa
Borussia Dortmund possible starting lineup:
Burki; Can, Hummels, Akanji; Meunier, Bellingham, Witsel, Guerreiro; Sancho, Reus; Haaland
We say: Lazio 1-3 Borussia Dortmund
With Dortmund boasting considerably more experience at this level of European competition, and heading into the match in considerably better form than their opponents, we think they have enough to start their campaign with a win.
Haaland being rested at the weekend should allow him to make several runs in beyond which will terrify a suspect Lazio backline. They conceded four at home to Atalanta earlier in the season and Dortmund are capable of doing similar offensive damage on their day.