Despite the well-documented association between innovation and business performance, many organizations struggle in their attempts to become successful innovators. This article discusses a recommended “art and science of transformation” approach to help companies improve their innovation performance through effective organizational change. The approach is focused on four key factors: culture, collaboration, strategy, and systems. Examples are drawn from a review of previous research to demonstrate successful innovation practice using similar approaches and examples of less successful practices are included to highlight ways in which an “art and science” approach can help overcome the difficulties often faced. The article concludes with some practical, step-by-step guidance based on the art and science of transformation framework.