Multi-cluster tools are widely adopted in semiconductor manufacturing. When a process module (PM) at a step fails, a multi-cluster tool cannot complete the process recipe of work-in-process wafers and must be forced to enter a closedown process to be empty. To increase the throughput of a wafer fab, it is economically significant to shorten the failure-closedown process. However, due to the wafer residency time constraints, it is highly challenging to respond to a PM failure and find a corresponding optimal schedule. By assuming no parallel PM at a step, this work is the first to study this important issue for scheduling multi-cluster tools. We analyze the task sequences and synchronization conditions for robot activities to avoid deadlock in a shared buffer module. Upon these analyses, for process-dominant multi-cluster tools whose optimal steady-state schedule is known, algorithms are proposed to synthesize the proper sequences for robots in case of PM failures, then, a nonlinear program model is proposed to find an optimal schedule for the corresponding closedown process or decide no feasible solutions. The proposed model can uniformly deal with different scenarios of PM failures. Examples are given to illustrate the application of the proposed method. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —In a wafer fab, there are hundreds, even thousands, of cluster tools. It is common that a failure of a processing module happens in a cluster tool. How to intelligently respond to such a random failure in a multi-cluster tool is an important issue in real-world production. This paper studies the scheduling problem of a multi-cluster tool in case of a failure at a PM. For a multi-cluster tool in case of a failure module, the proposed method can significantly reduce the loss of work-in-process wafers and shorten the closedown process.