The sides go head-to-head in San Pedro Sula on Wednesday with the South Americans having won just one of their last 14 games on the road.
Manuel Plasencia will take charge of Venezuela, having been placed in interim charge of the national side following Cesar Farias' departure to coach Liga MX outfit Tijuana in December.
Honduras are in good form on home soil, having beaten the United States and drawn with Mexico on their way to Brazil 2014, and will have extra cause for a win as the game will also act as a send-off for Victor Bernardez.
After a decade with the national team, the defender will retire from international football after the World Cup, meaning Wednesday's clash will be his last on home soil for Honduras.
And he is determined to go out in style with victory over Venezuela.
He said: "I'm motivated, it's my last game here at home before the World Cup, my colleagues do not want me to retire, but it is a decision already made with my wife and family.
"It's my last game in Honduras with the selection.
"We do not care what is said outside, this is a test and we will take it seriously."
Honduras striker Carlo Costly, the side's second-top scorer in World Cup qualifying, is absent with an ankle injury, so the hosts' hopes will likely rest of Jerry Bengtson.
The New England Revolution striker hit nine goals in the campaign and will hope to take the chance to impress with World Cup places up for grabs.
Despite having 92 caps to his name, midfielder Wilson Palacios also misses out, joining experienced winger Edgar Alvarez in the international wilderness.
Plasencia has named an experimental squad of 20 players for the game, leaving the likes of captain Juan Arango, Tomas Rincon and Salomon Rondon at home.
Four players could make their international debut in the fixture, including midfielder Pedro Ramirez - who has been in fine form for Venezuelan Primera Division leaders Zamora and striker Dany Cure - who plays his club football at Caracas, under Plasencia's management.
