After a year in which President Donald Trump has largely avoided a direct confrontation with Moscow, Tillerson used his final press conference in the role of top US diplomat to reiterate warnings issued by several military and intelligence officials in recent months about the need to confront "the troubling behavior and actions on the part of the Russian government."
"Russia must assess carefully as to how its actions are in the best interest of the Russian people and of the world more broadly. Continuing on their current trajectory is likely to lead to greater isolation on their party, a situation which is not in any one's interest," Tillerson said.
US officials have been sounding the alarm in recent months about Russia's growing multidimensional threat to US interests abroad and at home ranging from fears of widespread election interference to aggressive military posturing.
The task of navigating complex diplomatic challenges posed by Moscow now falls to Trump's soon-to-be former CIA director Pompeo.
Trump praised Pompeo on Tuesday saying he was "always on the same wavelength" -- something that he could not say for his departing chief diplomat Tillerson.
Pompeo, a politically astute former Republican congressman, has been careful to align himself with Trump in public on key issues, as has UN envoy Nikki Haley, and they will form a tight and combative foreign policy team.
There are questions about how Pompeo will approach Russia.
At the Aspen Security Conference in July, Pompeo was criticized for misrepresenting findings about Moscow's meddling in the 2016 election in a way that aligned with Trump's tendency to downplay the interference.
Pompeo said the "intelligence community's assessment is that the Russian meddling that took place did not affect the outcome of the election," when the intelligence community did not, in fact, make that assessment. Instead, it concluded that Moscow hacked conducted the hacking campaign to "help (Trump's) election chances."
And while Pompeo has since said there's no doubt about Russia's meddling, he also raised eyebrows by setting aside sanctions on senior Russian spymasters to allow them to come to the US and meet with him at the CIA.
Trump has cast doubt on accusations of Russian meddling. He has questioned whether the Russians were responsible for hacking the Democratic National Committee, and he has called the entire "Russia story" a hoax perpetuated by angry Democrats. He even convinced Pompeo to personally meet with a conspiracy theorist who denies that Russia hacked the DNC.
"That is an obvious concern," said Sen. Dianne Feinstein, a California Democrat, "because they appear to be very close and I know he does the (Presidential Daily Briefing)."
Referring to Pompeo's upcoming confirmation hearing before the Senate Foreign Relations Committee, she said, "I think he is going to have some tough questions in the committee. We'll see. Secretary of state is a whole different leaning. It's the ability to work with people, work with countries, know countries, travel to those countries. Develop relationships that can produce productive results for the United States."
"This is very different and it will be a different committee," Feinstein said. "I will say that the jury is out for me."
The departure of Tillerson may mean that Mattis will carry more of the load when it comes to US foreign policy and national security objectives, CNN national security analyst James Clapper said on Tuesday.
Asked by CNN's Jake Tapper about the overhaul of Trump's top advisers, Clapper said, "The leader I think a lot about ... is Jim Mattis."
"He probably carries a heavier burden not only in this country but overseas," Clapper added.
Earlier this year, the Pentagon named Russia as a near peer "great power" in its national military strategy, opening the door for the US to design and build new nuclear weapons it believes will deter Russian nuclear aggression.
"They've been building weapons, testing weapons, building weapons to operate from the earth in space, jamming weapons, laser weapons, and they have not kept it secret," Gen. John Hyten, the head of US Strategic Command, told an audience at the Reagan National Defense Forum in Simi Valley, California.
"They're building those capabilities to challenge the United States of America, to challenge our allies, and to change the balance of power in the world," added Hyten, who oversees all US military operations in space. "We cannot allow that to happen."
Russia's defense ministry said this week that it has successfully tested one of the "invincible" missiles that President Vladimir Putin said could deliver a warhead at hypersonic speed and pierce US defenses.
"Russia still has the greatest nuclear potential in the world, but nobody listened to us," Putin said in an annual address to the Russian Parliament earlier this month. "Listen now."
While Mattis has expressed skepticism at Russia's claims of having developed such high-tech missiles, saying such technology is "still years away," Putin's claim is just part of a broader effort to bolster the image of Russia's resurgent military might beyond its nuclear capability.
The Russian military continues to expand its presence in the Middle East, build up conventional and nuclear "capable" weapons on NATO's eastern front and challenge US strategic goals around the world.
Those efforts are perhaps no more evident than in Syria.
Last month Gen. Joseph Votel, who oversees all US troops in the Middle East, noted Russia's increasing strategic influence in Syria, telling lawmakers that Moscow is playing the role of "both arsonist and firefighter" in war-torn nation.
"Diplomatically and militarily, Moscow plays both arsonist and firefighter: fueling tensions among all parties in Syria, the Syrian regime, Iran, Turkey, the Syrian Democratic Forces, the United States and other coalition partners, then serving as arbiter to resolve the disputes, attempting to undermine and weaken each party's bargaining positions," Votel told a hearing of the House Armed Services Committee.
On Tuesday, America's top military officer, Gen. Joseph Dunford, spoke with his Russian counterpart Gen. Valery Gerasimov -- on the same day Gerasimov threatened to target US forces in Syria should they retaliate against the regime's use of chemical weapons.
Mattis warned Syria against using chemical weapons Sunday, implying it would prompt military consequences, as it did last year when Trump ordered a strike on a Syrian air base.
CNN's Barbara Starr, Stephen Collinson and Nicole Gaouette contributed to this report.