In 1623, after entering the Chinese empire at Guangzhou, Cardim settled in Macau. From 1626 until 1629, he lived in the Ayutthaya Kingdom, where he learned enough of the Thai language to write a catechism and a small treatise on the Christian faith. Together with Pedro Morejón and Romão Nishi, Cardim founded the Jesuit mission in Ayutthaya in 1626. They built a church there, in which they administered the sacraments to hundreds of residents of that city. In 1629, he returned to Macau to inform the local authorities about problems at the mission in Ayutthaya. In February 1631, Cardim was sent to Tonkin along with Miguel Matsuda and Pedro Kasui, where they were received with honor by King Trịnh Tráng. Learning of the existence of the Kingdom of Lan Xang, Cardim wanted to go to explore the possibility of establishing a mission there. However, the King of Ayutthaya would not allow Cardim to enter Lan Xang from Ayutthaya. Cardim later tried to enter through Tonkin, but fell seriously ill and was forced to return to Macau. In Macau, Cardim served as rector of St. Paul's College from August 1632 to May 1636. Elected prosecutor of the region in 1638, he went to live in Rome. He remained there for several years and participated in the Eighth General Congregation of the Society of Jesus which elected Vincenzo Carafa as the 7thSuperior General of the Society of Jesus. Back in his native Portugal, Cardim received strong support from King John IV for the missions. Cardim translated some of his works from Latin into Portuguese and Italian, and composed several important monographs on the missions of the Society of Jesus. Notable among these is Fasciculus e Japponicis floribus, which was first published in 1646. The book contains detailed accounts of at least 54 of the Christians martyred in Japan from 1597 through 1640. The book also contains, in addition to eighty-eight engravings, a detailed map of Japan. In 1640, four Portuguese ambassadors who had gone from Macau to Nagasaki were called upon to renounce their faith, and when they refused they were executed without further trial. Thirteen of their followers were sent back to Macau with this warning: "While the sun warms the earth let no Christian be so bold as to enter into Japan. Let this be known to all men. Though it were the King of Spain in person or the God of the Christians or Shakya himself, whosoever will disobey this prohibition will pay for it with his head." Cardim documented this episode in Mors felicissima quatuor legatorum Lusitanorum quo Japponiae Imperator occidit in odium Christianae religionis, which was first published in 1646.
On April 15, 1649, he boarded São Lourenço, a galleon which was subsequently wrecked off the coast of Portuguese Mozambique, where he passed the following winter. He finally arrived back in Goa at the end of May 1650. He wrote a report on his travels, entitled Batalhas da Companhia de Jesus na sua gloriosa provincia do Japão, which he dedicated to King John IV. On June 15, 1652, during the crossing from Goa to Macau, his ship was intercepted off Dutch Malacca by Dutch privateers and he was subsequently held prisoner for two years and seven months. After his ransom was paid, he finally arrived at Macau, exhausted by the long and arduous adventure. Cardim died in Macau on April 30, 1659, at 63 years of age.