We were made to pay for a disjointed start as Mitchell Curry fired Boro in front 24 minutes in, with the same player capitalising on a defensive mistake to extend the visitors' lead shortly after the interval.
Marcus Edwards gave us hope with a close-range finish, but Arnel Jakupovic settled the issue just after the hour mark and a miserable night was completed when defender Japhet Tanganga was sent off in stoppage time for hauling back the counter-attacking Harrison Chapman as the last man.
It was the lads' first competitive match since the IMG Cup Final in Florida on December 20 and the frustrating opening spell we endured was reflective of that lack of recent game time.
Chapman curled a free-kick marginally wide with less than two minutes gone, while Jakupovic latched onto one of a number of stray passes but shot off target from 20 yards out.
We still couldn't find our rhythm as we approached the quarter-of-an-hour mark with a lot of throw-ins conceded by both sides, while our first shot in anger came in the shape of a Charlie Owens free-kick that drifted over the bar on 14 minutes.
Chapman tried his luck with a header – off target – and a shot that was straight at goalkeeper Alfie Whiteman before we fashioned a good chance on the counter-attack as Jaden Brown's cross was blocked with Edwards then setting up Samuel Shashoua, but he couldn't keep his effort down and it flew behind.
We were lucky not to concede on 23 minutes when Marcus Tavernier split our defence clean open with a through pass and Curry zipped clear but, bearing down on goal, hit the base of the near post.
Curry made no mistake 60 seconds later, though, again finding space in the left channel and advancing at speed before thumping beyond the helpless Whiteman to give Boro the lead.
The goal seemed to spark us into life and we started to get the ball down and play with Keanan Bennetts particularly menacing on the right side of our attacking midfield set-up.
Lee Hetherington did manage to find an opening for the visitors but dragged across the face of goal from a tight angle on the right, but if anyone looked like conjuring up something in the run-up to half-time it was that man Bennetts. He turned onto his left foot at the right-hand corner of the box and sent a curling shot towards the top corner on 41 minutes, but Aynsley Pears in goal positioned himself smartly to catch it before it crossed the line.
Bennetts advanced down the right once again two-minutes later and tried to cut back for Joe Muscatt, but Boro were able to clear their lines.
We came out determined at the start of the second period but were hit by a sucker-punch on 50 minutes when a defensive slip-up gifted possession to Chapman and he picked out Curry in space in the box to slot home the second goal for Middlesbrough.
There was almost a breakthrough for us four minutes later when Owens sent in a wide free-kick and a back-header from Ryan Loft coaxed a fine save from Pears at close quarters.
Pears was there again on 58 minutes, making another excellent stop to keep out Bennetts' volley at the back post from Shashoua's cross, but he was beaten a minute later as more good work by Shashoua on the left saw Brown send the ball into the box with Edwards on hand to finish from close range.
It had become more of an open game by that point with Pears out to grab the ball at the feet of Loft, but Boro struck the killer blow on 61 minutes. Muscatt appeared to have secured a goal kick when tracking Chapman to the byline but the Boro wide man kept the ball in play and sent in a dangerous low ball that seemed to catch us by surprise. Christian Maghoma, back in defence after a loan spell at League Two Yeovil, instinctively scooped the ball out but only as far as the unmarked Jakupovic, who produced a composed finish from inside the box to restore the visitors' two-goal cushion.
The introduction of Charlie Hayford brought us some fresh attacking impetus down the right – his first action of the game coming in the form of a looping cross that saw Loft force a save from Pears with a header.
Middlesbrough weren't prepared to sit on their lead though and kept coming at us, Tavernier's effort spinning just wide with Whiteman called upon to thwart Jakupovic shortly afterwards.
Chapman broke forward at pace on 79 minutes but Maghoma slid in to block before Whiteman denied Jakupovic again with a flying save after Curry's effort was charged down at the edge of the box.
Loft went close with a downward header at the other end, Pears scrambling down low to his left to turn the ball behind, while substitute Nick Tsaroulla was just off target as he attempted to put the finishing touch to a fine move that he started himself.
Time was running out, though, Whiteman saving from Curry on the angle as the size of the task at hand become ever more apparent and our night was typified when Boro counter-attacked one final time and last defender Tanganga was shown a straight red card for hauling back Chapman as he tried to go through.
There was still time for Tsaroulla to try another shot which was blocked away for a corner, but the night belonged to the visitors.
Spurs: Whiteman, Muscatt (Hayford 67), Brown, Owens, Tanganga, Maghoma (c), Bennetts (Tsaroulla 80), Stylianides, Loft, Edwards (Sterling 67), Shashoua. Substitutes (not used): Duncan, McDermott (GK).
Middlesbrough: Pears, Hegarty, Coulson, Tavernier, McGoldrick, Cook, Curry, Pattison, Jakupovic, Hetherington, Chapman. Substitutes (not used): Wilson, Convery, Renton, Reading, Dawson (GK).