When the Apostle Paul finally arrived in Rome, he met with the Jewish leaders there and explained his situation to them. “Then they said to him, ‘We neither received letters from Judea concerning you, nor have any of the brethren who came reported or spoken any evil of you. But we desire to hear from you what you think; for concerning this sect, we know that it is spoken against everywhere'” (Acts 28:21-22, NKJV). Paul spent two years under house arrest in Rome and according to 2 Timothy 4:16 appeared before Caesar Nero, but was not convicted. Then, as far as anyone knows, he was released and allowed to continue his ministry.
It is clear from Acts 13:1-21:17 that Paul went on three missionary journeys. There is also reason to believer that he made a fourth journey after his release from the Roman imprisonment recorded in Acts 28. The conclusion that such a journey did indeed take place is based on: (1) Paul’s declared intention to go to Spain (Romans 15:24,28), (2) Eusebius’s implication that Paul was released following his first Roman imprisonment (Ecclesiastical History, 2.22.2-3) and (3) statements in early christian literature that he took the gospel as far as Spain (Clement of Rome, Epistle to the Corinthians, ch. 5; Actus Petri Vercellenes, chs. 1-3; Muratorian Canon lines 34-39). (Paul’s Fourth Missionary Journey, pgs. 1738-1739)
The reason Luke didn’t include Paul’s fourth missionary journey in his book of Acts may have been because he thought Paul’s arrival in Rome signified the accomplishment of the goal of his ministry. Another reason may have been because Luke left Paul in Rome and didn’t know what happened to him. Paul stated in 2 Timothy 4:16, “At my first answer no man stood with me, but all men forsook me: I pray God that it may not be laid to their charge.” Paul went on to say, “Notwithstanding the Lord stood with me, and strengthened me; that by me the preaching might be fully know, and that all the Gentiles might hear: and I was delivered out of the mouth of a lion” (Acts 4:17). “Since as a Roman citizen, Paul could not be thrown to the lions in the amphitheater, this must be a figurative way of saying that his first hearing did not result in an immediate guilty verdict” (note on Acts 4:17).
Although the details of Paul’s final arrest and death by execution are not included in the Bible, it is believed that his second letter to Timothy was written shortly before he was beheaded in Rome. In that letter, Paul disclosed that “only Luke is with me” (2 Timothy 4:11). If Luke and Paul were separated after his first imprisonment in Rome, they were reunited sometime before his death around 67 or 68 A.D. Paul concluded his second letter to Timothy with these final words, “The Lord will rescue me from every evil assault, and He will bring me safely into His heavenly kingdom; to Him be the glory forever and ever. Amen.” (2 Timothy 4:18, AMP).