Background: As role substitution models gain prominence in healthcare, understanding the factors shaping their effectiveness is paramount. This study aimed to investigate factors that impact the implementation and performance evaluation of professional role substitution models in healthcare, with a focus on understanding the variables that determine their success or failure in adoption, execution, continuity, and outcomes. Methods: The exploratory qualitative study used semi-structured interviews with key opinion leaders, decision makers, facilitators, recipients, and frontline implementers, who had influence and involvement in the implementation of professional role substitution models. Data analysis was guided by the Consolidated Framework for Implementation Research (CFIR). Results: Between November 2022 and April 2023, 39 stakeholders were interviewed. Factors influencing implementation and evaluation of allied health professional role substitution models of care aligned with the five core CFIR domains (innovation, outer setting, inner setting, individuals, implementation process) and outcome domain incorporating implementation and innovation outcomes. The six themes identified within these CFIR domains were, respectively; i) Examining the dynamics of innovation catalysts, evidence, advantages, and disadvantages; ii) Navigating the complex landscape of external factors that influence implementation and evaluation; iii) Impact of internal structural, political, and cultural contexts; iv) The roles and contributions of individuals in the process; v) Essential phases and strategies for effective implementation; and vi) The assessment of outcomes derived from allied health professional role substitution models. Conclusions: The study highlights the complex interplay of contextual and individual factors that influence the implementation and performance evaluation of professional role substitution models. It emphasises the need for collaboration among diverse stakeholders to navigate the challenges and leverage the opportunities presented by expanded healthcare roles. Understanding these multifaceted factors can contribute to the development of an empowered workforce and a healthcare system that is more efficient, effective, safe, and sustainable, ultimately benefiting patients.