Shalom was born in Gabès, Tunisia on 4 August 1958 to a family that traced its roots to the Sephardic Beit Shalom dynasty. His family made aliyah to the city of Beersheba, in Israel's Negev in 1959. On 3 November 1964, while Shalom was six years old, his father, Shimon Shalom, a bank manager and a member of the Betar movement, was killed during the course of a bungled bank robbery. The murder was notoriously known as the first committed in a bank robbery in the history of the young state of Israel. At the age of 18, Shalom was inducted into the Israel Defense Forces and achieved the rank of Sergeant.
After completing his service in the IDF, Shalom attended Ben-Gurion University of the Negev in Beersheba, from which he received a BA in economics and earned his certification as a CPA. During that time, Shalom was elected as the chairman of the university's students' union and later as the vice chairman of the national students union. He later attended Tel Aviv University, from which he received an LLB law degree as well as an MA in public policy. Shalom began his career as a journalist. While working on his first degree, he wrote for Yedioth Aharonoth, a daily newspaper, in its students section. Afterwards he started working at the "Rosh Berosh" magazine and in the Negev's local newspaper. In 1980, he moved to Tel Aviv and started working at the now-defunct daily Hadashot. In 1984, he was appointed as its head political and economic correspondent.
In 1992, at the age of 34, Shalom was 34th on the Likud list for the 13th Knesset, but the party received only 33 seats in the elections. When former Defense MinisterMoshe Arens resigned, Shalom succeeded him as an MK.
As a young MK, his first bill was in the academic field. In 1992 there was room for only 100,000 university students, with no space for more. Shalom acted to allow all students to be accepted once others left their academic institutions at the end of their first year. His bill increased awareness about the problem and, as a result, Israeli colleges were established to expand access to academic studies. In 2010, for the first time, more students were enrolled in colleges than universities. Shalom, during his first term, was the first male MK to be a member of the Knesset's committee on the status of women. He was also the chairman of the subcommittee regarding the capital market, chairman of the subcommittee of energy and a member of the economic affairs committee.
Following the 1996 election, Shalom, who won the 18th spot in the combined list of Likud and two other conservative parties, became Deputy Defense Minister, Yitzhak Mordechai. One of his biggest achievements was enabling Hareidi Jews to serve in the army, a step that they had been avoiding for decades. The Hareidi battalion, "Netzah Yehuda", was established on February 1999.
After a rotation with MK Michael Eitan, Shalom, on July 13, 1998, became Minister of Science. During his year in office he created the "science flowers" project, which helped universities reach Israel's periphery and helped underprivileged students excel. Another main project Shalom was involved in was in expanding Internet and broadband access in Israel and as a result, surfing speed.
In the 1999 election, the Likud party, headed by the widely unpopular prime minister at the time, Benjamin Netanyahu, was running against the Labor party, headed by Ehud Barak. Labor won 26 seats in the Knesset, while Likud received only 19 seats and lost the election. After Labor gained power in 1999 and following Netanyahu's resignation, Shalom, became number one on the Likud list and became part of the opposition, lead by Ariel Sharon.
Shalom was the runner-up to Netanyahu for party leadership in late 2005 and was granted the second spot on the Likud list to the 2006 general election and thus did not compete in its January 11, 2006 primaries. He was placed seventh on the party's list for the 2009 elections.
Shalom is married to Israeli talk show host Judy Shalom Nir-Mozes. The couple have five children and reside in Ramat Gan. On March 24, 2014, a woman complained that he sexually harassed her at work 15 years before. He was cleared several months later by the Attorney General.