The COVID-19 pandemic and other ongoing public health challenges have highlighted deficiencies in the US public health system. The United States is in a unique moment that calls for a transformation that builds on Public Health 3.0 and its focus on social determinants of health and partnerships with diverse sectors while also acknowledging how the pandemic altered the landscape for public health. Based on relevant literature, our experience, and interviews with public health leaders, we describe seven areas of focus within three broad categories to support transformational change.