The foundation was created in 2018 following the sale of Fidelis Care,[2] a private nonprofit health plan that was incorporated by New York State's Catholic bishops in 1993.

[5][2] It provided grants to around 500 organizations and initiatives,[2] including Gates Vascular Institute and the John R. Oishei Children's Hospital.

[6] In 2020, the foundation committed an additional $50 million of funding, specifically to support COVID-19 related programs that would help New Yorkers affected by the virus.

[15] In 2022, the Foundation provided $2 million in funding for FoodMap NY, a project focused on long-term solutions for food insecurity, including support for farmers in New York state.

[27] It was named for Mother Frances Xavier Cabrini, a Roman Catholic nun who founded the Missionary Sisters of the Sacred Heart of Jesus and was the first naturalized American citizen to be canonized a saint.

[27] Grants from the foundation are provided to initiatives and organizations that support underserved and low-income communities in New York State and aim to improve healthcare and quality of life, specifically social determinants of health.