Following UEFA's overhaul, the competition's format will mirror that of the Champions League, meaning these sides face seven more games between now and early next year.
Match preview
Dynamo will take their place in this season's new-look Europa League, having lost in the Champions League qualifying playoffs last month, falling 3-1 on aggregate to RB Salzburg.
They were unable to overcome a two-goal deficit after losing the first leg, playing out a 1-1 draw in Austria one week later, but the consolation of entry into Europe's second-tier competition at least softened the blow.
The Ukrainian giants had previously seen off Partizan Belgrade and Rangers to reach the final hurdle, having missed out on an automatic Champions League place after failing to take top spot in Ukraine last term.
Oleksandr Shovkovskyi's side finished two points adrift of champions Shakhtar Donetsk, but they have already started their quest to regain the title with five wins from six - and they are still undefeated atop the Ukrainian Premier League table.
In their last 11 games in the old Europa League group stage, Dynamo drew five and lost six, with their last victory coming almost five years ago. They are also yet to beat Lazio in four competitive meetings, so they will try to put both records right on Wednesday.
Lazio have won both previous away games against Dynamo to date: in the Champions League group stage 25 years ago, and then in the second leg of a 2018 Europa League last-16 tie. On the latter occasion, goals from Lucas Leiva and Stefan de Vrij secured victory in Ukraine.
This time, instead of travelling to Kyiv, the Rome club will head to Hamburg, where Dynamo are hosting European fixtures this season due to the ongoing conflict in their homeland.
Lazio come into this contest amid some inconsistent form in Serie A, where they occupy eighth place in the standings after five matches.
Having celebrated a 2-1 home victory over former club Hellas Verona last Monday, new boss Marco Baroni returned to his hometown of Florence at the weekend, seeking three more points against Fiorentina.
However, a pair of Albert Gudmundsson penalties - the second coming in second-half stoppage time - overturned Mario Gila's opener at Stadio Franchi and Lazio headed back to the capital empty-handed.
Gila's goal did maintain their scoring streak though, as the Biancocelesti have found the net for 13 straight games since firing a blank versus arch-rivals Roma back in April.
Dynamo Kiev form (all competitions):
L
D
W
W
W
D
Lazio form (all competitions):
Team News
Marco Baroni's chief concerns relate to his attacking department, as not only did former Lazio captain and last year's four-goal leading Champions League scorer Ciro Immobile leave in the summer, but two first-choice forwards now face a race to be passed fit.
Argentinian striker Taty Castellanos limped out of last Monday's match with a muscular issue, before Boulaye Dia - who had scored on his first two starts for the club - picked up an ankle injury at the weekend.
New skipper Mattia Zaccagni is therefore set to feature in a front line with any three from Gustav Isaksen, Tijjani Noslin, ex-Spain star Pedro and Loum Tchaouna.
Isaksen has been involved in seven goals in 14 Europa League appearances to date, netting both home and away against Lazio in 2022 and effectively persuading them to sign him from FC Midtjylland.
Dynamo's attack will be led by veteran striker Andriy Yarmolenko and young colleague Vladyslav Vanat, with Panama international Eduardo Guererro most likely used from the bench.
Meanwhile, Volodymyr Brazhko and Mykola Shaparenko should be joined by Oleksandr Pikhalyonok in central midfield.
Dynamo Kiev possible starting lineup:
Bushchan; Karavaev, Popov, Mykhavko, Dubinchak; Brazhko, Shaparenko, Pikhalyonok; Yarmolenko, Vanat, Kabayev
Lazio possible starting lineup:
Mandas; Lazzari, Gila, Romagnoli, Tavares; Rovella, Guendouzi; Isaksen, Pedro, Zaccagni; Noslin
We say: Dynamo Kiev 1-1 Lazio
Aside from one off-day against Salzburg, Dynamo have played pretty well in Europe this season, while Lazio are coming straight into the league phase off the back of some mixed domestic form.