Spence has been designing jewelry and custom leather works from a very young age. She was taught by her grandmother, Fabiola Spence. Her inspirations include her Cree heritage, urban culture, and vibrant colours and elements. In 2007, Spence released the fashion line Designs by Rosary which includes fashion and footwear, graphic apparel, jewelry, and accessories. In 2014, Spence designed limited-edition footwear and contributed original footwear as a Storyboot Artist for Manitobah Mukluks. In 2015, Spence joined Indigenous apparel brand Urban Nish as a brand ambassador and design consultant. In 2017, Spence joined the international eyewear company, Dreamcatcher Eyewear, as a designer.