Claudio Ranieri must prepare his charges for the visit of a winning machine, after both sides got the year off to contrasting starts - defeat for Samp and a thumping win for Inter.
Having had a hit-and-miss campaign so far, hat-trick hero Lautaro Martinez led the Inter cavalry on Sunday as they laid waste to promoted Crotone's flimsy defence, easily racking up an eighth straight league win - their best streak since 2008.
A crushing 6-2 victory - albeit after surprisingly going behind early on - kept the pressure on city rivals AC Milan at the top of the Serie A table.
Heavily involved in two of Martinez's three strikes, star striker Romelu Lukaku made his 50th Serie A appearance for Inter at the weekend, also scoring his 50th goal in all competitions.
In doing so, the prolific forward joined exalted company, as only five other players have scored more goals than his 35 in their first half-century of league games during the three-points-for-a-win era: Cristiano Ronaldo (with 40), Ronaldo (38), Andriy Shevchenko (37), Diego Milito (37) and Vincenzo Montella (36).
Although Lukaku's involvement on Wednesday appears in doubt because of a thigh problem picked up at San Siro, others in the squad are capable of picking up the slack.
Antonio Conte's offensive department have registered 24 goals in the last eight games - averaging three goals per game - for a team who rarely look fluent but are often ruthlessly effective.
Sampdoria's hopes of a positive start to 2021 were washed away in the torrential rain on Sunday, as Edin Dzeko's second-half winner for Roma saw them defeated by a single goal at Stadio Olimpico to sit 11th in the table.
Despite their inherent inconsistency, Samp boss Ranieri claims he does not expect new signings in the January transfer window, insisting that the future return from injury of forwards Manolo Gabbiadini and Keita Balde will suffice.
While that demonstrates the constraints Ranieri is working under in Genoa and the limited ambitions of his latest club in a long and distinguished career, the one-time Premier League winner undoubtedly has some raw talent at his disposal.
Scandinavian stars Morten Thorsby, Mikkel Damsgaard - plus the evergreen Albin Ekdal - offer reason to hope for a top-half finish this term, as they have provided a touch of thrust and incision to the Sampdoria counter-attack.
However, Ranieri's men have been found wanting defensively too often this term and the Blucerchiati have failed to keep a clean sheet since October - so the visit of in-form Inter will be laced with fear for a brittle back four.
Sampdoria Serie A form: LLWWLL
Inter Milan Serie A form: WWWWWW
Inter Milan form (all competitions): DWWWWW
Top scorer Lukaku, who suffered a thigh strain against Crotone, is expected to miss out for Inter, so Lautaro Martinez will be joined by the returning Alexis Sanchez - injured for much of the season himself.
Talented youngster Mikkel Damsgaard is entrusted to play in support of the Senegal striker, with Inter old boy Antonio Candreva starting out wide.
Due to suspension, Albin Ekdal is unavailable, so Adrien Silva and Thorsby will man the Sampdoria engine room.
Sampdoria possible starting lineup:
Audero; Bereszynski, Yoshida, Tonelli, Augello; Candreva, Thorsby, Silva, Jankto; Damsgaard; Balde
Inter Milan possible starting lineup:
Handanovic; Skriniar, De Vrij, Bastoni; Hakimi, Barella, Brozovic, Gagliardini, Young; Martinez, Sanchez
We say: Sampdoria 1-2 Inter Milan
Since their ignominious exit from Europe last month, no team has been able to resist Inter's unstoppable form. Demonstrating Antonio Conte's characteristic steeliness, the Nerazzurri have shot up the standings.
Certainly, a lightweight Sampdoria side should hold few concerns for the Scudetto challengers, though it may not be an entirely straightforward march to victory at Marassi on Wednesday.