WATCH Paris-Roubaix Femmes LIVE, FREE and in HD on SBS and SBS On Demand this Saturday, April 16 from 9:30pm (AEST).
Vos finished second in last year's inaugural edition, trailing only Lizzie Deignan who soloed to victory in epic fashion.
It was a heart-breaking loss for Vos, who did her best to track Deignan down but ultimately fell just over a minute short, with Elisa Longo Borghini closely behind in third.
The nature of the defeat has not been lost on the Dutchwoman, who decided against defending her Amstel Gold crown last weekend out of full focus on the Queen of the Classics.
Deignan's absence, one brought about by the birth of her second child, only amplifies Vos' cause and the Jumbo-Visma veteran believes no stone has been left unturned in her preparation.
"I'm fit, I'm really looking forward to it," Vos said, as quoted by Cyclingnews.
"The tyre pressures have been tested extensively, and we are well prepared as a team."
A field full of contenders will do their best to deny Vos victory, not least of which is Elisa Balsamo; the Trek-Segafredo star set to receive full support from Australian Chloe Hosking and Borghini.
Balsamo fell victim to last year's mud-soaked conditions and will hope her next attempt will be without the kind of crash she needed a full week to recover from in 2021.
The fairer conditions may help her, but rival Lotte Kopecky certainly won't as the SD Worx rider aims to build on victories in both the Strade Bianche and Tour of Flanders.
Kopecky will fancy her chances on the familiar terrain, as will teammates Chantal van den Broek-Blaak and Elena Cecchini who, too, have carried form over to the 125-kilometre course.
Movistar's Emma Norsgaard is another name in the running, though much will depend on the tactics employed and the cobbled sections stretching 29.2 kilometres in total.
Nine riders from last year's top 10 will take to the start line on Saturday night, and while Deignan is the only omission, it's clear Vos' bid to build on her legendary list of accomplishments will be far from a procession.