Pompeo arrived on Tuesday for talks with Indian leaders in New Delhi where he is expected to tackle a host of delicate issues from trade to India's longstanding defense and energy ties to Russia and Iran.
Pompeo landed in New Delhi late on Tuesday night after an unannounced trip to Kabul.
He will kick off his visit to India by calling on Prime Minister Narendra Modi who was re-elected for a second term last month.
Just ahead of his visit, New Delhi imposed tariffs on some U.S. goods after President Donald Trump's administration threw India out of a group of countries that were allowed duty free access for some of their products into the large U.S. market.
Washington has also threatened to impose sanctions on Turkey, a NATO ally, which is also buying the S-400 system.
Under U.S. pressure, India has stopped buying oil from Iran, one of its top suppliers, and the two Indian officials said the oil-dependent economy had taken a hit as a result.
Now, with tensions rising between the United States and Iran, New Delhi is further worried about the security of its energy supplies.