The Belgian was forced to come off in the 6-2 trashing of Crotone at San Siro last weekend due to a muscle injury in his leg.
With the Nerazzurri due to face Roma at the weekend, boss Antonio Conte may not risk further damaging the injury, and opt to give Lukaku a rest against Sampdoria.
Latest reports suggest that Croatian Ivan Perisic could get the nod to partner Lautaro Martinez up front, at the expense of Alexis Sanchez.
Defensively, Inter are expected to line-up with the same three central defenders as they did against Crotone, with Milan Skrinriar, Alessandro Bastoni and Stefan De Vrij all due to start.
Chilean midfielder Arturo Vidal could be dropped for the game, after his poor display against Crotone. Conte could be hard repeatedly shouting at Vidal, and it's likely that he will be on the substitute bench for the game.
Nicolo Barella, Marcelo Brozovic are expected to start, and Roberto Gagliardini could be the one to replace Vidal in central midfield.
Achraf Hakimi and Ashley Young are expected to retain their places in the starting XI in the wing-back positions.
Stefano Sensi could come off the bench for Inter should things get difficult at the Stadio Luigi Ferraris. Want-away midfielder Christian Eriksen isn't likely to feature.