Bou struck a hat-trick and set up Racing's opening goal away to Tachira, while Milito finished the match with a goal and two assists, as the Argentinian Primera Division side powered their way to victory in Venezuela.
In Racing's first Copa Libertadores match since 2003, Luciano Lollo opened the scoring in the 21st minute with a flick from Bou's free-kick.
It was 2-0 by half-time with Bou playing a one-two with Milito before crashing his volley past Tachira goalkeeper Alan Liebeskind.
Bou further extended the visitors' lead seven minutes after the break with another stunning goal, bringing down Sebastian Saja's goal-kick at the top corner of the box and, with his second touch, thumping the ball inside the far post.
Milito scored the fourth goal soon after, beating Liebeskind in a one-on-one, while Bou - in his first Copa Libertadores appearance for Racing - wrapped up the Argentinian club's win in the 69th minute. The 25-year-old striker tapped in Milito's cross.
Tachira's Jorge Rojas missed a penalty four minutes from time.
The victory took Racing to the top of Group Eight with Guarani set to host Sporting Cristal on Wednesday.
Elsewhere on Tuesday, Wanderers came from behind twice to defeat Zamora 3-2 at home in a match marred by five red cards.
Visitors Zamora had Angel Faria sent off after just 19 minutes but took the lead six minutes later.
Wanderers lost Adrian Colombino in the 31st minute but levelled the match in first-half stoppage time.
Zamora would lead again eight minutes into the second half but Luis Ovalle was red-carded with 12 minutes left for conceding a penalty and Nicolas Albarracin equalised from the spot.
Leandro Reymundez struck the winner for Wanderers in the 82nd minute before each team copped another red card in stoppage time - Jorge Murillo and Juan Mascia receiving their marching orders.
In Group Four, The Strongest and Emelec both won with the former cruising past Internacional 3-1 in La Paz, with the visitors losing Nilmar to a red card with a minute left.
Alejandro Chumacero notched a brace for The Strongest, who claimed top spot in their group, while Emelec prevailed 1-0 at Universidad de Chile.
Also on Tuesday, Santa Fe won 1-0 at Atlas.
