Both sides took time to settle into the game on a cold, wet and windy afternoon in Berkshire.
It was Boro who settled first and edged into the lead with nine minutes played when Marcus Tavernier picked up where he left off against Blackburn last week. This time instead of Mikael Soisalo (away on international duty), it was Bradley Fewster who he set up as the striker tapped home with nine minutes played.
That sharpened the focus of the home side who had one shot deflected over the bar, then a few minutes later Matty Elsdon was in the right place at the right time to block a Joseph Mendes shot on the line.
The Royals had built up a head of steam by the time they drew level with 36 minutes played.
Boro had offered stoic resistance and attacked where possible, but were undone when Ryan East set up Joseph Mendes who struck home low under Aynsley Pears.
The hosts went close again as they closed the first half strongly with Tyler Frost firing just wide.
Half-time Reading U23s 1 Boro U23s 1
It didn't take Reading long to turn their superiority into goals.
In the first minute of the second half Gabriel Osho tucked in from close range after a header from Royals' skipper Robert Dickie had been turned on to the bar.
A classy goal from Joseph Mendes gave the hosts a two goal cushion on 64 minutes and Boro had it all to do.
A double change saw Ben Liddle and Hayden Coulson replaced by Liam Hegarty and Lewis Maloney and a few minutes later Tavernier rounded off a neat approach with a shot that flashed just wide.
Boro had rallied from a worse position in their previous away game at Brighton, could they do it again?
An 86th minute volley from Yakou Meite answered the question, a close-range volley whistling home for the Royals fourth of the afternoon and a passage in to tomorrow's quarter-final draw.
Boro need to pick up quickly. Their next game is a North Riding Senior Cup semi-final away to Whitby on Thursday night, 7.45pm.
Reading: Legg; Watson, Dickie (Capt.), Osho, Richards, East, Meite, Rinomhota, Mendes, Frost, Novakovich (Barrett 89). Subs: Medford-Smith, Driscoll, Holsgrove, Smith.
Boro: Pears; McGhee (Capt.). McGoldrick, Elsdon, Torrajon, Liddle (Hegarty 70), Mondal, Pattison, Fewster, Tavernier (Wheatley 81), Coulson (Maloney 70). Subs: James (gk); O'Neill.
Referee Mr C Hicks
Yellow card Richards, 79, foul