The Giallorossi had failed to beat their city rivals in their previous five meetings - including a 1-0 loss in the Coppa Italia final back in May - but triumphed 2-0 on Sunday thanks to goals from Federico Balzaretti and Adem Ljajic.
"It was a very important game for us and for our fans," Roma coach Rudi Garcia said. "As I said before the game, you don't play a derby, you win it."
Roma go into the encounter at the Stadio Luigi Ferraris looking for their fifth consecutive win.
The Giallorossi have 12 points and sit joint top of the standings with Napoli, who host bottom side Sassuolo on Wednesday.
Garcia's men have looked solid at both ends of the pitch, scoring 10 times while conceding only once.
And, unlike Napoli, Roma are not competing in Europe this season and can focus solely on domestic matters.
Garcia is keeping his feet firmly on the ground, saying: "Our objective is to finish in the top five and get back into the European competitions.
"I too am ambitious, but it is too early to say anything more than that.
"We haven't played enough games to know our true level, but I really like this team and our fans."
Samp, meanwhile, have taken just two points from the 12 on offer.
Last weekend's 2-2 result at Cagliari followed a 3-0 defeat to Genoa in the Derby della Lanterna.
The Blucerchiati have won just one of their last 15 league games and Delio Rossi's men are desperate to stop the rot.
"We will go into the game against Roma determined to do well and to get a positive result," Samp midfielder Lorenzo De Silvestri said.
"We know it will be difficult because we face one of the best teams in the competition and that is why we need to play a perfect game."