The Italy international scored twice to help Rudi Garcia's men to a comfortable home-win, with Miralem Pjanic also finding the back of the net
Mattia Destro gave the Giallorossi the lead in the closing stages of the first half, before Miralem Pjanic made it two after the break, with Destro adding his second and Roma's third to seal the victory.
The visitors started the match the better side of the two and Eder had a good chance to hand his side the lead midway through the first half. Angelo Palombo set up the attacker with a fine through ball, but he failed to beat Morgan De Sanctis.
Roma grew into the game and created two chances to break the deadlock on 30 minutes. Firstly Gervinho threatened, only for Daniele Gastaldello to come to the rescue for Samp, before a smart Pjanic shot was kept out by Angelo Da Costa.
De Sanctis was called into action again only minutes later as Lorenzo De Silvestri found Roberto Soriano, but the Roma goalkeeper showed his class with a fine save.
Kevin Strootman should have opened the scoring shortly before the break after some poor defending from Palombo, only for the Netherlands international to fire straight at Da Costa from close range.
Roma did go ahead in the closing stages of the first half, though, via Destro. The striker beat his marker to the ball to meet a Alessandro Florenzi corner and left Da Costa with no chance to make it 1-0.
Rudi Garcia's men kept on pushing for more after the break and they did not need long to double their lead. The referee awarded the hosts a free kick in a dangerous position and Pjanic beat the Sampdoria goalkeeper with an accurate strike over the wall.
Things only got worse for the away side shortly after as Destro made it three for Roma. Gervinho found the former Inter youngster with a low pass inside the area and the striker had no trouble finding the net from close range.
Sampdoria were then reduced to 10 men toward the end of the game as Gastaldello was shown his second yellow card of the evening for a foul on Radja Nainggolan.
Roma sit second in the league table with 54 points from 23 games, trailing leaders Juventus by nine points, but with a game in hand.
The Giallorossi resume Serie A action on Saturday when they travel to Bologna.