In Friday's other Group B match, North Korea host Bahrain in Pyongyang hoping to boost their qualifying campaign following a 2-1 defeat in Japan last month.
In Group A, 2002 World Cup semi-finalists South Korea travel to Saudi Arabia in an intriguing clash of styles and Kuwait host Uzbekistan.
Japan's visit to Tehran should provide the fireworks with Iran chasing their first win after drawing 0-0 in Bahrain in their opening final round qualifier.
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Japan won last year's Asian Cup amid a hostile atmosphere in China but the cauldron-like Azadi Stadium will be new to many players.
For those in the squad who played for J-League side Jubilo Iwata in the 1999 Asian club championship it will bring back uncomfortable memories.
"It was weird," midfielder Toshiya Fujita said. "They were throwing stones and tomatoes...all sorts of things. At one point a dead pigeon just missed me."
Japan coach Zico came under fire after his team's somewhat fortunate victory over North Korea in their Group B opener but he insists his players will not be intimidated.
"Playing at home or away is just the same," said the Brazilian. "As a player, I loved playing in that kind of intense atmosphere in front of 100,000 people. I expect the players to rise to it."
Playmaker Hidetoshi Nakata will return to Japan's side for the first time in a year, along with fellow Europe-based midfielders Shinji Ono and Junichi Inamoto.
Iran's Croatian coach Branko Ivankovic is confident a full-strength Japan squad will hold no fears for his side.
"We don't care about the opposition...if they are Germany, North Korea or Japan," he shrugged. "The crowd will give us an advantage. They will be like a 12th man for us."
South Korea coach Jo Bonfrere also welcomes back his Europe-based contingent for Friday's visit to Dammam following a 1-0 warm-up victory over Burkina Faso.
"It's a must-win game but we have the ability to win it," said PSV Eindhoven's Park Ji-sung. "If we play like we did in the first match we should be alright."
South Korea top Group A after beating Kuwait 2-0 in their opening game and victory over Saudi Arabia, thrashed 4-1 by Finland at the weekend, would put them firmly in control.
The pressure is on the Saudis following a 1-1 draw with Uzbekistan in Tashkent last month.
All eight teams are in action again next Wednesday. The top two from each group qualify automatically for next year's World Cup in Germany.
Asia could earn a fifth spot as the two third-placed teams meet for the right to contest a two-legged playoff against a CONCACAF side.
Follow LIVE scoring of the Asia zone World Cup qualifiers on from 07:35 on Friday.
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