Chronic wounds are an unmet clinical need affecting millions of patients globally, and current standards of care fail to consistently promote complete wound closure and prevent recurrence. Disruptions in growth factor signaling, a hallmark of chronic wounds, have led researchers to pursue growth factor therapies as potential supplements to standards of care. Initial studies delivering growth factors in protein form showed promise, with a few formulations reaching clinical trials and one obtaining clinical approval. However, protein-form growth factors are limited by instability and off-target effects. Gene therapy offers an alternative approach to deliver growth factors to the chronic wound environment, but safety concerns surrounding gene therapy as well as efficacy challenges in the gene delivery process have prevented clinical translation. Current growth factor delivery and gene therapy approaches have primarily used single growth factor formulations, but recent efforts have aimed to develop multi-growth factor approaches that are better suited to address growth factor insufficiencies in the chronic wound environment, and these strategies have demonstrated improved efficacy in preclinical studies. This review provides an overview of chronic wound healing, emphasizing the need and potential for growth factor therapies. It includes a summary of current standards of care, recent advances in growth factor, cell-based, and gene therapy approaches, and future perspectives for multi-growth factor therapeutics.