Freddy Eastwood did halve the deficit for a short time, before a goal from Mido settled the outcome of this encounter once and for all.
Jenas nearly unlocked Southend's defensive gate on 11 minutes when his surge forward took him clear before his measured pass inside the area into the path of Keane was the subject of a last ditch interception.
Later in the same minute the lead was secured when Zokora went on the charge from his own half and did manage to pick out Keane, who drilled in on goal and the ball took a significant deflection off of Steven Hammell and Darryl Flahavan was left stranded in the Southend goal.
Aaron Lennon then brilliantly played in Hossam Ghaly, who proceeded to leave his marker staring at turf, before squaring for Keane who did not really do justice to the quality of the move with his attempt on goal.
Lennon was providing a regular stream of threatening crosses from the left flank, while Jenas was looking his old self in midfield, covering the ground, linking play, supporting attacking sorties and doing his share defensively. His energy in midfield probably has been missed over the last six weeks or so.
He brilliantly bought Keane into play at the half hour mark from one of his sprints forward, with the striker hitting the feet of the goalkeeper with his low drilled shot from a tight angle. His next opening was the result of a speedy counter-attack that began with debut boy Ricardo Rocha dispossessing Jamal Campbell-Ryce, then Zokora bring the ball quickly out. It was next out right to Stalteri, who crossed low and Keane cut across his marker to direct towards goal and it took a superb save from Flahavan to tip over the crossbar.
The boys were two goals to the good on 48 minutes when Lennon seized the ball off of Lewis Hunt and embarked on a mazy run which led to him dispatching a teasing cross over over the six yard box and Jenas was in place to guide the ball in and make it a happy return to the side.
Radek Cerny - in for the rested Paul Robinson - was soon forced into a smart save to deny Kevin Maher a goal on his second return to the Lane, before Flahavan did likewise at the other end to stop Jenas bagging a another. Mido came close to adding his name to scorers with a header from a measured Jenas throughball, while Keane could have increased his tally after good work from Lennon and Zokora.
Southend's travelling army were celebrating after 68 minutes when Hossam Ghaly was penalised for handball while the process of clearing a deflected free-kick. It looked an incredibly harsh call, but Freddy Eastwood stuck the penalty home all the same.
Steed Malbranque was added to the mix for the final 17 minutes in place of Ghaly and on 75 minutes the two-goal advantage was restored when Jenas picked out the run of Lennon down the right and the winger zapped the ball into the near post with considerable power and Mido stole in front of his markers and the ball fired up and landed over the line via the underside of the crossbar.
Mido was off complaining over a back problem with five minutes left on the clock and we were left with a changed shape with Defoe - already on for Keane - up top, with Jenas and Malbranque in support. There were no more goals, but there is the 5th round draw on Monday to look forward to now.
Progress to the 5th round of the FA Cup was achieved with an impressive 3-1 victory over Southend United at the Lane on Saturday.In front of a crowd of 33,406, Robbie Keane opened the scoring in a first half that should really have yielded more goals, while Jermaine Jenas marked his restoration to the side after injury with a goal that was the very least his performance deserved.