Andrea Stramaccioni's young side saw lots of the ball but lacked quality in the final third as the Russians' ruthlessness sees them progress as champions of their pool
Karadeniz Gokdeniz's second-minute opener and Salomon Rondon's double in the latter stages of the match highlighted the gulf in efficiency between the two teams in Russia.
With qualification already wrapped up, Andrea Stramaccioni opted to field a youthful XI for the trip to the Tsentralnyi Stadion, handing the likes of Andrea Romano, Marco Benassi and Isaac Donkor their Nerazzurri debuts.
However, it was one of their first-team stars who was guilty of gifting Rubin the go-ahead goal. With just two minutes on the clock, Alan Kasaev's cross was guided onto the post by Juan Jesus, allowing Karadeniz to tap home the rebound.
Philippe Coutinho was given another chance to stake his place in the Inter side, but could not string together a clear-cut chance for the visitors in the first half, while Marko Livaja again failed to convince he is an able deputy for Diego Milito.
A scrappy opening period soon came to an end, with little in terms of enterprise being demonstrated by either outfit, and Stramaccioni threw on captain Javier Zanetti and European goal hero Rodrigo Palacio in an attempt to inject some much needed dynamism.
It looked like an inspired pair of substitutions as Inter began to take control of the match, and in one instance the Argentine forward interchanged with Andrea Ranocchia in a probe towards the Rubin box, but saw his lot shot cannon off the post.
Unfortunately for the Italians, the hosts had an ace of their own up their sleeves in form of Rondon. Berbas Natcho's hooked pass over the Inter defence was latched onto by former Malaga striker, and he outmuscled Donkor to net for 2-0.
And later on yet more salt was rubbed in the wounds of Stramaccioni's young side, as Karadeniz drifted into the box from the right-hand side and drilled in a low cross for Rondon to tuck home from a matter of yards out.
The result leaves Rubin top of Group H and three points clear of the Serie A giants with one round of matches remaining, but their superior head-to-head record means they progress as leaders of the pool.