The Milan club lost to Sampdoria 1-0 on Sunday to remain rooted to midtable on the league standings
Inter travelled to the Luigi Ferraris stadium looking to build on a 2-1 mid-week win over Torino that saw Argentine striker Mauro Icardi put two goals past England 'keeper Joe Hart.
But Sampdoria had other ideas, and when Fabio Quagliarella swept a loose ball past Samir Handanovic on the stroke of half-time Inter were left with a mountain to climb.
They resumed in determined fashion after the break, but Icardi squandered arguably their best chance of the half on 67 minutes when he glanced a header wide from Marcelo Brozovic's cross.
De Boer, who was given the backing of the club's new Chinese owners last week despite reports he is facing the sack, made a double substitution with 15 minutes remaining.
Eder and Antonio Candreva were replaced on the right and left sides of a three-man attack with Rodrigo Palacio and Ivan Perisic.
Sampdoria came close to doubling their lead, Handanovic coming to the rescue to block Ante Budimir after he was sent through by Bruno Fernandes four minutes from the end.
De Boer's changes almost paid off in the dying minutes of injury-time as Inter poured forward, but after latching on to Perisic's delivery, Palacio, who had stumbled to the ground, saw his effort come off the crossbar.
Inter sit in 11th place and are now 13 points behind leaders Juventus, who, after a 2-1 win over Napoli on Saturday, hold a four-point lead on Roma.