Objectives: New models for the workforce are required in long-term care(LTC) homes, as was made evident during the Coronavirus Disease 2019 (COVID-19) pandemic. Nurse Practitioner (NP)-led models of care represent an effective solution. This study explored NPs’ roles in supporting LTC homes as changes in directives, policies, and recommendations related to COVID-19 were introduced. Design: Qualitative exploratory study. Context: Thirteen NPs working in LTC homes in Ontario, Canada. Methods: Semi-structured interviews were conducted in March/April 2021. A five-step inductive thematic analysis was applied. Findings: Analysis generated four themes: leading the COVID-19 vaccine rollout; promoting staff wellbeing related to COVID-19 fatigue; addressing complexities of new admissions; and negotiating evolving collaborative relationships. Conclusions: Nurse practitioners were instrumental in supporting LTC homes through COVID-19 regulatory changes producing unintended consequences. The NPs’ leadership in transforming care is equally essential in LTC homes as in other established healthcare settings, such as primary and acute care.