To maintain and enhance innovation performance, many firms nowadays look for resources from external sources such as strategic alliances and regional network embeddedness. While considering the important interdependencies among different alliances, research has established an alliance portfolio perspective. From an alliance portfolio perspective, firms can consciously configure the dimensions of their alliance portfolios such as partner characteristics, relational properties, or structural properties. However, within the context of alliance portfolio configuration , the role of regional networks has been largely overlooked. As most high-tech firms are regionally clustered, this is an important research gap. In addressing this gap, this study explores the link between regional network density, alliance portfolio configuration, and its contribution to firm innovation performance. We examine how regional network density and alliance partner diversity influences firm level innovation output. We also investigate the moderating effect of overall network partner status and partner diversity on the link between regional network density and innovation performance. Our empirical evidence is derived from a longitudinal quantitative study of 1,233 German biotechnology firms. We find that regional network density and alliance partner diversity has an inverted U-shape effect on firm level innovation performance. However, overall network status as well as alliance partner diversity negatively moderates the link between regional network density and innovation output. Thus, our study contributes to a better understanding of the link between regional networks, alliance portfolio configuration, and firm level innovation performance.