Both teams are adrift of safety with 10 games left to go, and any side suffering defeat in Genoa will surely say goodbye to their place in the Italian top flight.
Match preview
Having lost only one of their 13 Serie A meetings with Cremonese in the past - including a 1-0 victory in October's reverse fixture - Sampdoria must surely maintain their dominant record in this fixture to keep slim hopes of survival alive.
Samp's win at Stadio Zini last autumn was the first of just three throughout the whole 2022-23 campaign, and the only one in which they have kept a clean sheet.
Though the third arrived in another relegation battle before the international break, when they came out on top against fellow strugglers Verona, last week saw Dejan Stankovic's side sustain a harsh body blow, after they held top-four contenders Roma goalless for nearly an hour but then folded when Jeison Murillo was given his marching orders.
Conceding three times after the Colombian's dismissal, they left Rome empty-handed and therefore sit 10 points behind 17th-placed Spezia with games fast running out to avoid demotion to Serie B.
Also faced by impending financial ruin, the 1991 Scudetto winners are enduring a miserable time both on and off the field; yet there remains the dimmest flicker of hope that a miracle can be achieved at Marassi.
Upcoming clashes with Cremonese, Lecce and Spezia could define Samp's season - for better or worse - and if they can beat the former this week, to secure back-to-back home wins for the first time in nearly a year, the Blucerchiati faithful will still believe.
The only side sitting below Sampdoria in the standings, Cremonese's abject position of being 12 points shy of safety means that, in all probability, their Serie A comeback is set to last a single season: defeat to Atalanta last week was their 17th in the league.
The only bright spot in a difficult campaign for the Lombardy club has been a remarkable cup run, which saw both Napoli and Roma eliminated in the earlier rounds ahead of Wednesday's semi-final first leg against Fiorentina - Italy's most in-form side.
Hopes of lifting a first-ever Coppa Italia receded, though, after the pair clashed at Stadio Zini, as Davide Ballardini's men were beaten 2-0 without laying a glove on the vibrant Viola.
An uphill battle awaits, then, in the return leg - to be played in Florence later this month - but between now and then Cremo must take as many points as possible from games against Samp, Empoli and Udinese.
Successfully starting that task on Saturday would defy their previous away form, as only Verona have picked up fewer points on the road than Cremonese in Serie A this season - just seven, and each from a draw.
Indeed, the Grigiorossi are one of only four teams - along with Stuttgart, Verona and Almeria - to remain winless away from home in Europe's top five leagues this term.
Sampdoria Serie A form:
L
L
D
L
W
L
Cremonese Serie A form:
D
W
L
L
D
L
Cremonese form (all competitions):
W
L
L
D
L
L
Team News
Sampdoria will have to make another change in their defence this weekend, after Jeison Murillo stepped in to replace the suspended Bram Nuytinck in the Blucerchiati's back three against Roma, only to be sent off himself.
Roles should be reversed, then, on Saturday, though Koray Gunter offers another option for Dejan Stankovic if he can return to fitness in time. Meanwhile, in goal, Nicola Ravaglia was selected instead of Martin Turk last week and should continue to deputise for injured first-choice Emil Audero.
Having scored 44% of his club's league goals this season, Marco Gabbiadini starts up front, most likely supported by Filip Djuricic and Michael Cuisance, with Mehdi Leris operating on the right flank. Either Sam Lammers or Jese Rodriguez would start instead, should Stankovic go for a more traditional front two.
Following the demands of their Coppa Italia tie in midweek, Cremonese could make some changes, perhaps starting in goal: against Fiorentina, Mouhamadou Sarr surprisingly started rather than established number one Marco Carnesecchi, but the latter should now return.
In the second half of the Grigiorossi's defeat, Cristian Buonaiuto and Cyriel Dessers were introduced as Davide Ballardini switched to an unfamiliar 4-3-3, but a more recognisable three-man defence is expected to line up at Marassi.
Luka Lochoshvili could feature in that rearguard after being benched on Wednesday, as both Vlad Chiriches and Samp-owned loanee Alex Ferrari remain unavailable; Emanuel Aiwu's upcoming suspension only applies to the cup.
Veteran striker Daniel Ciofani (six goals) is Cremo's top scorer in the league and has found the net in both of his last two top-flight appearances. In David Okereke's continued absence, he could start again in Genoa, but Dessers is also in contention.
Sampdoria possible starting lineup:
Ravaglia; Zanoli, Nuytinck, Amione; Leris, Winks, Rincon, Augello; Cuisance, Djuricic; Gabbiadini
Cremonese possible starting lineup:
Carnesecchi; Vasquez, Bianchetti, Aiwu; Sernicola, Galdames, Pickel, Meite, Valeri; Dessers, Tsadjout
We say: Sampdoria 2-1 Cremonese
Deflated by their defeat in the Coppa Italia, Cremonese also tend to run out of steam during the closing stages of games, so will be vulnerable to an improving Sampdoria side on Saturday.