An excellent negotiator, Moffitt put his plan into motion by first proposing the idea to Hollis Boren, then dean of the University of South Florida College of Medicine.

"Out of that discussion came plans for a plug-shaped, multilevel cancer research teaching hospital to be built a short walk away from the USF clinics," The Tampa Times reported on February 5, 1979.

In 2022 the Florida Legislature approved more than $706 million for a new H. Lee Moffitt Cancer Center and Research Institute campus in Pasco County.

This expansion includes the Vincent A. Stabile Research Building, eponymously named in recognition of the largest private donation ever made to the Cancer Center.

In 2008, the University of Florida and Shands at UF formed a partnership with Moffitt to develop programs in cancer care, research and prevention.

[15][16] Scientific programs include molecular oncology;, drug discovery; immunology; experimental therapeutics; computational biology of cancer; health outcomes; and behavior and risk assessment, detection and intervention.

Moffitt Cancer Center is affiliated with the University of South Florida Morsani College of Medicine and provides education to medical students and residency training as well.

Services on the site include the skin and breast cancer clinics, four operating rooms, an imaging suite, research labs, space for blood draws and a Publix pharmacy.

[24] In July 2017, Moffitt and Memorial Healthcare announce a partnership to establish a comprehensive blood and marrow transplant cellular therapy program for South Florida residents.

The alliance brings the renowned cancer center's access to research, clinical trials, and comprehensive treatment to leukemia, lymphoma and multiple myeloma patients.

[26] Through clinical trials, Jeffrey Weber, director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt, and researchers at Moffitt Cancer Center discovered two monotherapy drugs – Mekinist (trametinib) and Tafinlar (dabrafenib) – can be safely combined to overcome or delay treatment resistance for a large percentage of melanoma patients with a specific gene mutation.

[29] In September 2014, a new cancer immunotherapy for melanoma patients called Keytruda became the first anti-PD-1 (programmed death receptor-1) therapy approved in the United States.

Jeffrey Weber, director of the Donald A. Adam Comprehensive Melanoma Research Center of Excellence at Moffitt, was one of the lead investigators of the clinical trial which led to the drug receiving breakthrough status from the FDA.

[30] In January 2016, researchers at Moffitt teamed up with the state of Florida in a study to see if making fruits and vegetables available to children who otherwise may not have them readily available can decrease their risk of cancer.