This study extends the knowledge of the human resource management (HRM)–innovation relationship and examines how innovation‐facilitating bundles of HRM practices are applied to facilitate radical pharmaceutical front‐end innovation (FEI). The empirical investigation is an explorative case study of science‐driven FEI and HRM practices across one in‐depth case study and seven validation studies among international pharmaceutical and biotech companies. The findings provide a theoretical overview of key HRM practices in support of radical pharmaceutical FEI as well as an empirical mapping of how innovation‐facilitating bundles of HRM practices are applied to actively develop radical, science‐driven pharmaceutical FEI, including the identification of the key innovation challenges and opportunities involving innovation‐facilitating HRM practices in pharmaceutical FEI. The article contributes to the existing innovation literature in terms of identifying how radical FEI may be facilitated through the application of innovation‐facilitating bundles of HRM practices. The empirical contribution and managerial implications provide nine specific suggestions for how pharmaceutical management groups can better support radical pharmaceutical FEI through targeted HRM practices. The derived results of the study also underline inherent challenges of the pharmaceutical industry and regulations (FDA) that may not stimulate radical innovation, which cannot be resolved by HRM, but require the attention of policy makers. The value added lies in the specificity of the empirical, pharmaceutical context in which the issue of supporting radical, science‐driven FEI is investigated.