The Belgian turned home Gonzalo Higuain's cross before firing in a free kick as Rafa Benitez' side narrowed the gap to second-place Roma.
The Belgian attacker swept home from close range after being set up by Higuain before firing home a deflected free kick later in the second half.
Sampdoria battled well for stages and will rue efforts from Manolo Gabbiadini and Nicola Pozzi that somehow failed to cross the line after smashing against the woodwork, but ultimately the Partenopei were able to seal a valuable win on their return from the winter break.
Raffael earned a start in goal with Pepe Reina unavailable, while Dries Mertens was named in attack as Marek Hamsik continues his recovery from injury for Napoli.
In a lively start, Mertens called Angelo Da Costa into action as he cut inside and fired at the near post, before Higuain wasted the best of the early chances as he volleyed straight at the keeper from point-blank range after Anthony Reveillere's cross.
Nenad Krsticic then combined well with Eder to tap home but the goal was correctly ruled out for offside, before Higuain turned inside the area and fired across goal, with Mertens inches from connecting on the slide.
Napoli continued to press hard, Mertens and Higuain both scuffing shots wide before Jose Callejon turned inside Lorenzo De Silverstri only to place his effort over the bar. Eder then volleyed high and wide on the turn before Insigne just failed to convert Higuain's cross as the match rather fizzled out heading into the halftime break.
Sampdoria started the half brightly, with Eder twice calling Raffael into action, but Napoli broke the deadlock soon after. Callejon slid the ball through to Higuain, who cut back into the path of Mertens to sweep home in style.
Gabbiadini came within inches of levelling after rifling a shot off the crossbar, but the home side doubled its advantage just after the hour mark. Mertens, often guilty of poor set-piece delivery during the match, fired a free kick from 25 yards that took a slight touch off the wall to evade Da Costa and find the net.
Insigne then wasted a great chance as he fired over when free inside the area, before Mertens headed wide from a corner.
Substitute Pozzi then contrived to hit both posts with a curling left-footed shot before Insigne shot just wide late on as Napoli narrowed the gap to Roma in relatively comfortable fashion.