Uncertainty is an inherent factor that affects all dimensions of supply chain activities. In today’s business environment, initiatives to deal with one specific type of uncertainty might not be effective since other types of uncertainty factors and disruptions may be present. These factors relate to supply chain competition and coordination. Thus, to achieve a more efficient and effective supply chain requires the deployment of innovative optimization models and novel methods. This preface provides a concise review of critical research issues regarding innovative supply chain optimization models with multiple uncertainty factors. It also introduces the special issue’s research papers and their respective insights.