The Nerazzurri extended their solid run of form, which has seen them win three and draw one of their last five games, to climb into the top four.
Star striker Icardi netted a first-half hat-trick and then added to his tally early in the second period, as Inter piled more misery on European-chasing Sampdoria following their 4-1 loss at Crotone last time out.
A dominant Inter soon edged in front through Perisic's looping header from 10 yards, sparking what would prove to be an onslaught.
Having failed to find the net since the start of January prior to today, Icardi scored the first of a 14-minute hat-trick on the half-hour mark from the penalty spot after Rafinha was bundled over.
The Argentina international's second came via a backheel from inside the six-yard box, and the third soon followed as he blasted the ball home after Viviano parried it into his path.
Sampdoria, who had earlier hit the bar through a Duvan Zapata attempt, found themselves five behind just six minutes into the second half as Icardi sent a half-volley into the ground and over Viviano.
Half a chance came and went for Antonio Candreva to add to the scoring, but his miss from a promising position would ultimately not matter, with Inter cruising through the remainder of the match to remain in Champions League contention.
Sampdoria (4-3-1-2): Viviano; Bereszynski (Verre 34'), Silvestre, Ferrari, Murru; Barreto (Regini 54'), Torreira, Praet; Ramirez (Caprari 50'); Quagliarella, Duvan Zapata
Inter Milan (4-2-3-1): Handanovic; Cancelo, Skriniar, Miranda, D'Ambrosio; Gagliardini, Brozovic; Candreva (Vecino 78'), Rafinha (Valero 80'), Perisic; Icardi (Eder 66')