Contributing to the scarce literature on how companies can deal with their business model of digital transition, this work explores the digital transformation (DT) process in small and medium enterprises (SME), investigating how organizational culture, structure, and leadership influence it. While such three factors are deemed essential components to facilitate DT, how they operate and how they relate to each other are still not very well-defined issues in need of in-depth investigation. This study employed a mixed-methods approach, following an exploratory sequential design. First, a conceptual model was developed based on qualitative data collected from expert interviews and analyzed through grounded theory. This stage uncovered 25 first-order concepts about culture, structure, and leadership, further organized into 6 constructs and hypothesis paths. Then, with a sample of 192 SMEs, the structural model was measured and validated using exploratory factor analysis and PLS-SEM. As a result, our study offers robust and timely research, whose conceptual model condenses a knowledge corpus that future research can benefit from, and it provides statistical extrapolations about how and how much those factors relate to each other in SME context; moreover, given the traditional scarce resources and lack of flexibility in SMEs, it provides orientation and guidelines to managers facing DT and needing to understand the organizational factors they should be aware of, where to focus energy, and what to expect as results. From a large-scale perspective, this study carries an impactful contribution to the many countries where SMEs play a major economic and social role.