"It is very easy to receive a pat on the shoulder from the international community, to bow one's head," Netanyahu said on Sunday at a candle-lighting ceremony in Rome's main synagogue which he visited with Letta.
"I would like to dispel any illusions. Iran aspires to attain an atomic bomb. It would thus threaten not only Israel but also Italy, Europe and the entire world," he was quoted as saying on his website.
"There should be no going astray after the attack of smiles. Today there is a regime in Iran that supports terrorism, facilitates the massacre of civilians in Syria and unceasingly arms its proxies," he said.
Netanyahu later on Monday will be received for the first time at an audience by Pope Francis, who is expected to travel to the Middle East next year.
Israeli sources say the visit could take place before Israeli President Shimon Peres ends his term in July. Although no date has been made official, sources on both sides say it is likely to take place on May 25th and 26th.
Israel and the Vatican first established full diplomatic relations in 1993, but have been engaged in years of thorny diplomatic negotiations over property rights and tax exemptions for the Catholic Church, which have yet to be fully resolved.
Netanyahu and Francis are also expected to discuss negotiations between Israel and the Palestinians, which resumed in July after a three-year hiatus but have faltered due to Israeli plans for new settlement building.
Netanyahu will then hold a meeting with Letta and a joint press conference is expected at around 1400 GMT.
Iran has agreed to curb its nuclear programme for the next six months in exchange for limited sanctions relief following marathon negotiations in Geneva last month.
But Israel, Iran's arch-foe, has slammed the deal as an "historic mistake" and US Secretary of State John Kerry is due in Israel this week to try to ease tensions.
Tehran has a long history of belligerent statements toward the Jewish state, and Israel - the Middle East's sole if undeclared nuclear power - has warned that a nuclear Iran would pose an existential threat.
"The most dangerous regime in the world must not be allowed to have the most dangerous weapon in the world," Netanyahu said on Sunday, adding that the sanctions regime on Iran was "liable to collapse".
US President Barack Obama's administration has argued that the preliminary deal will help ensure the security of the Middle East region as it seeks to nail down a comprehensive settlement with Iran.
Iranian President Hassan Rouhani, who was elected earlier this year, has promised a more diplomatic approach to the West after eight years of stalled talks and escalating sanctions under his hardline predecessor, Mahmoud Ahmadinejad.