The match will be Lazio's first time back on the pitch for nearly four months following the coronavirus-enforced shutdown, and Simone Inzaghi's side trail leaders Juventus by one point as things stand.
Atalanta picked up right where they left off in the Italian top flight as they recorded a comfortable 4-1 victory over Sassuolo on Sunday.
Gian Piero Gasperini's side had to make do without the prolific Josip Ilicic for the tie, but fellow striker Duvan Zapata netted a brace as Atalanta enjoyed their sixth win on the bounce in all competitions.
La Dea also progressed through to the Champions League quarter-finals for the first time in their history with an 8-4 aggregate victory over Valencia just before play was halted.
Gasperini's side have become widely renowned for their goalscoring exploits, having notched up 74 strikes from 26 Serie A outings - with Ilicic, Zapata and Luis Muriel all in the double figures for this season.
Atalanta are comfortably on course for a second consecutive top-four finish, but La Dera will need to be wary of Roma who are only six points behind and waiting to pounce on any slip-ups.
Similarly, Lazio will also enter this match in a strong position and will be looking to win their fifth match in a row when they travel to the Gewiss Stadium.
Inzaghi has witnessed his side relish in a terrific season in the Italian top flight, and Lazio are firmly in the running for a first Serie A crown since 2000.
I Biancocelesti are unbeaten in the division since September and have embarked on a remarkable run of 16 wins from their most recent 18 outings, including seven wins from their last eight on the road.
Furthermore, Inzaghi's side can boast the least amount of losses (two) and goals conceded (23) thus far, and top scorer Ciro Immobile is the firm favourite to collect the Capocannoniere after a particularly impressive campaign.
The Italian has chalked up 27 strikes in the league this term - six more than closest rival Cristiano Ronaldo - including a last-gasp penalty as Lazio rescued a point in a thrilling 3-3 draw with Atalanta back in October.
Atalanta Serie A form: WWWWWW
Atalanta form (all competitions): WDWWWW
Lazio Serie A form: WDWWWW
Mario Pasalic picked up his fifth yellow card of the season against Sassuolo and is suspended for the visit of Lazio.
Ilicic was forced to miss Atalanta's opening game back with a sprained ankle, and the forward is not expected to be fit in time for Wednesday.
Gasperini may revert to his tried-and-tested 3-4-1-2 formation against Lazio, potentially opening the door for Muriel to start alongside Zapata with Papu Gomez dropping into the number 10 role.
Jordan Lukaku has only appeared twice all season amid injury woes but has now made his return to training, although Wednesday's fixture will most likely come too soon for the Belgian.
Atalanta possible starting lineup:
Gollini; Djimsiti, Caldara, Palomino; Hateboer, De Roon, Freuler, Gosens; Gomez; Muriel, Zapata
Lazio possible starting lineup:
Strakosha; Patric, Acerbi, Radu; Lazzari, Milinkovic-Savic, Parolo, Alberto, Jony; Immobile, Correa
We say: Atalanta 2-2 Lazio
The clash between Atalanta and Lazio promises to be a fascinating match-up between two of the country's most exciting sides this season. Both teams are packed with attacking talent and will be desperate to pick up all three points, but we are struggling to pick a winner for this one.