Firefighters were called to Rejuvenate Hair and Skin on Shuter Street, Moonee Ponds, in Melbourne's north-west, about 12.50am on Wednesday.
Police spent the morning combing the scene, where a pair of singed jerry cans were propped outside the salon, which police believe were thrown inside before the business was set alight.
The offenders fled in a light coloured vehicle towards Puckle Street.
The hair and skin clinic's owner Hamidah Dildar, known to clients as Hannah, told AAP she was devastated her business of five years had been destroyed.
"This was my ultimate dream ... I poured my heart and soul into this," Ms Dildar said.
"I cannot think of any enemy or anyone not being happy with the service I provide and I have a great community of clients behind me."
It is the third time the Moonee Ponds business has been targeted by vandals in six months, after the shop's windows were smashed on two separate occasions.
"This time it's more severe, I'm really scared for my safety," Ms Dildar said.
"I feel like I have to start from zero, like I cannot stay in Victoria."
The Melbourne mother told AAP she had never received any threats related to her business and had no connections to the illicit tobacco trade.
The inferno was the second suspicious fire in the city's north-west overnight, after an unoccupied home on Deakin Street in nearby Essendon was engulfed in flames just before midnight.
Dozens of firefighters spent more than an hour trying to bring that blaze under control.
The home, which was gutted by the fire, was undergoing renovations.
Investigators were told at least one offender was seen fleeing the scene.
It is too early to determine if the fires are linked, police said.
The state is dealing with what authorities say is the fallout from illegal tobacco sales, with a spate of suburban firebombings involving young offenders.
There have been more than 150 tobacco store fires in Victoria since March 2023.
A statewide crackdown saw Victoria Police close 61 stores caught selling illicit tobacco, with alleged links to organised crime, over the past four weeks.
Yet, a string of firebombings and arson attacks has continued to sweep the city in the past week.
"You can have retailers who might not look like they're tobacco retailers but actually might still be selling these products," Deakin University criminologist James Martin told AAP.