Bedevilled by injuries in defence, the Biancocelesti seek to bounce back from having their winning run brought to an abrupt end last week, as Claudio Ranieri's inconsistent side come to the capital.
A momentum-breaking 3-1 defeat to new league leaders Inter last Sunday saw Lazio's streak of six consecutive victories come to a crashing halt at San Siro. Antonio Conte's men proved too clinical on the counter, as the Aquile could not translate their domination of possession into goals.
Now level on 40 points with both Napoli (who have a game in hand) and Atalanta, plus three behind city rivals Roma, who they ruthlessly decimated in the derby last month, Simone Inzaghi's side are under pressure to mount another run of results in Serie A to secure Champions League football next season - just as they are set to face defending champions Bayern Munich in this year's competition.
With perhaps one eye on their first-leg encounter in midweek, there is speculation that Inzaghi will rest some key men against Sampdoria, though a string of injuries at the back may limit the extent of any changes he can make in that department.
Though their seasonal record is similar both home and away, at the Olimpico lately, Lazio have won their last five outings - versus Napoli, Fiorentina, Roma, Sassuolo and Cagliari - and in three of those games they have also kept a clean sheet.
Furthermore, the Biancocelesti's most prominent attacking weapons have hit their straps in recent weeks, with influential midfielder Sergej Milinkovic-Savic being directly involved in 11 goals in Serie A this season (with 5 goals and 6 assists), only managing a better haul in the entirety of 2017-18, when he totalled 15.
Star striker Ciro Immobile has been in flying form too and has racked up a remarkable 12 goals in his 13 league games against Samp in the past - more than against any other opponent in the top flight. Certainly, on Saturday, the red-hot Azzurri striker will fancy his chances of adding to the five netted in his last two encounters with the Ligurian outfit.
Enjoying the stability of tenth place in the Serie A standings, sitting comfortably inside the top half with a five-point buffer over old foes Genoa, Sampdoria travel to Rome having suffered only one defeat - against champions Juventus - in their last five.
Last weekend, the Blucerchiati saw off Fiorentina at Stadio Luigi Ferraris, as veteran forward Fabio Quagliarella punished the visitors by coming off the bench to do what he does best - ending a rare seven-match scoring drought with his match-winning strike.
Also approaching veteran status, another Azzurri star of the past, Antonio Candreva, added an assist to his record. A contribution of five this season, allied to four league goals - despite having a spell out of the side due to a row with manager Claudio Ranieri - has offered a useful supply line to Samp's rotating cast of forwards.
Having scored in every away game but one this term, Sampdoria can also draw upon fond memories of their previous meeting with Lazio. Against all pre-match predictions, they triumphed 3-0 at Marassi in October, as top scorer Quagliarella scored the opener in the 32nd minute.
Ranieri's men will face a tough task next weekend against another Champions League contender, Atalanta, before preparing for a much-anticipated Derby della Lanterna clash with vastly improved city rivals Genoa the following week.
Notoriously unpredictable this season and having also previously downed both Atalanta and Inter, perhaps Samp will upset the odds once more on Saturday.
Lazio Serie A form: WWWWWL
Lazio form (all competitions): WWLWWL
Sampdoria Serie A form: LWWLDW
Simone Inzaghi has to negotiate a growing injury crisis in defence, just days ahead of Lazio's return to continental action, as Wesley Hoedt is suspended and Luiz Felipe - whose season was effectively ended last week - Stefan Radu and goalkeeper Thomas Strakosha are out injured.
In-form wing-back Manuel Lazzari is also suspended on Saturday, so Mateo Musacchio should be drafted in to central defence and Mohamed Fares or club captain Senad Lulic - who has struggled for opportunities since recovering from injury - will start on the left flank, with Adam Marusic switching to the right.
Sampdoria, contrastingly, have an almost full squad at their disposal, as long-term injury victim Manolo Gabbiadini has been involved in full training and is now nearing a comeback.
Keita Balde returns to his former club in fine form and will lead the line in Claudio Ranieri's XI, with Fabio Quagliarella favourite to partner him, though Gaston Ramirez could instead feature if the former Roma coach opts for a more cautious 4-4-1-1 setup.
The ongoing battle for places in the Samp engine room continues, with Morten Thorsby and Albin Ekdal competing to partner Adrien Silva in the centre, while Antonio Candreva will hope to usurp young Mikkel Damsgaard on the right wing as he also gets set to meet his former team, in the city of his birth.
Lazio possible starting lineup:
Reina; Musacchio, Patric, Acerbi; Marusic, Milinkovic-Savic, Escalante, Alberto, Fares; Correa, Immobile
Sampdoria possible starting lineup:
Audero; Bereszynski, Yoshida, Colley, Augello; Candreva, Silva, Ekdal, Jankto; Keita, Quagliarella
We say: Lazio 2-2 Sampdoria
Though Lazio have certainly improved of late, neither side has been rock-solid in defence this term, so the hosts' patched-up back three can definitely be breached on Saturday.
Samp have been a hard-to-call prospect, as they are just as likely to topple one of the top clubs as they are to falter against an also-ran. With their own key attackers finding form in recent weeks, the visitors should take advantage of the circumstances to bring a point home to Genoa.