Inter leapfrog Lazio into fifth to keep their Champions League dreams alive, while Sampdoria drop to 13th following the encounter at the Stadio Luigi Ferraris
The visitors opened the scoring on the verge of half-time as Rodrigio Palacio headed past Sergio Romero before adding a second late on to secure a vital three points.
Inter started brightly and could have taken the initiative in the opening few minutes, but Sergio Romero got down quickly to push the ball away from Palacio after the Argentine had beaten the offside trap and looked to round the Sampdoria goalkeeper before firing over.
Mauro Icardi then came close to breaking the deadlock on the 20-minute mark, having seen his near post header force Samir Handanovic into a smart save as both teams enjoyed an equal share of possession.
Handanovic was again forced into action with 10 minutes of the half remaining as the Inter goalkeeper tipped Nenad Krsticic's 25-yard effort over the bar.
The Nerazzurri opened the scoring minutes before half-time as Palacio met Alvaro Pereira's cross and the Inter striker did well to connect with the ball and head past Romero. The Argentine then came close to adding a second with a minute of the first half remaining, but dragged his effort narrowly wide of the far post.
The hosts began the second half strongly as Gianluca Sansone forced Handanovic into a neat save from the edge of the Inter 18-yard box with Sampdoria looking to drag themselves back into the encounter.
Shkodran Mustafi denied Palacio excellently on the 55th minute before a change of shape for Sampdoria saw the hosts look to stretch Inter as Pedro Obiang tested Handanovic from the edge of the box, but his effort was comfortably smothered by the Slovenian.
The Blucerchiati continued to press for an equaliser, with substitute Maxi Lopez testing Handanovic from a free kick, but the Inter goalkeeper held on comfortably.
Sampdoria continued to pressure the visitors, but came undone in the last minute of stoppage time as Palacio strode forward and fired under Romero to secure his side a vital victory.