Sandro played the first half with Kaboul, Paulinho and Vertonghen all playing to the hour mark. Tim Sherwood reported afterwards that all four came through unscathed.
Kaboul, sidelined since November 24 with a thigh problem and Vertonghen, out since December 4 with an ankle injury, lined-up together in central defence.
Paulinho, who damaged an ankle against Stoke on December 28 was alongside Sandro, who suffered a hamstring injury against Liverpool on December 15.
Brad Friedel, Kyle Naughton, Zeki Fryers, Etienne Capoue, Lewis Holtby, Gylfi Sigurdsson and Harry Kane also started at Upton Park.
Kane struck twice and saw another two goals disallowed and Holtby provided all three assists in what was a competitive encounter, but essentially a comfortable win.
Kane opened the scoring on 12 minutes. Picking the ball up centrally, he played a one-two with Holtby, drove forward and finished confidently one-on-one.
Friedel did well to save from Seb Lletget on 14 minutes but it was all Spurs for the remainder of the first half.
Kane was there to tap home after Sam Howes palmed out Holtby's low drive, but the offside flag was up. Howes did well to touch Sigurdsson's curler away from the top corner on 36 minutes but couldn't prevent us going 2-0 up minutes later as Holtby lofted a pass through to Paulinho, who blasted home from 16 yards.
Milos Veljkovic replaced Sandro at half-time and Kane was there again 10 minutes into the second half to slide in Fryers' cross, only to be denied by the flag again.
Giancarlo Gallifuoco, Kevin Stewart and Grant Ward replaced Kaboul, Paulinho and Sandro on the hour and the next action of note saw George Moncur scoop over from Lletget's cross.
Kane was finally rewarded with a second goal to make it 3-0 on 72 minutes. The move started with Sigurdsson's precise pass to Holtby inside the box, he unselfishly squared to Kane, who picked his spot from 10 yards.
The Hammers had a couple of late chances, Paul McCallum headed wide from close range and Friedel produced the save of the game in the final seconds, throwing himself full stretch to his right to fingertip away Shaun Maguire's curler destined for the top corner.
Spurs: Friedel; Naughton (A McQueen, 75), Kaboul (Gallifuoco, 60), Vertonghen (Stewart, 60), Fryers; Capoue, Paulinho (Ward, 60), Sandro (Veljkovic, 46); Holtby (Couleybaly, 75), Kane, Sigurdsson.
Below - Lewis Holtby congratulates Harry Kane after the striker made it 3-0 at Upton Park...