A system and method for automatically tuning a multiprocessor (MP) computer system having a set of processors, associated memory resources, interrupt sources and interrupt service routines (ISRs). Upon initialization of the MP system, the ISRs are assigned to the processors in a particular fashion. Thereafter, runtime statistics associated with the execution of the ISRs by the processors are monitored periodically. Where there is an imbalance with respect to a condition relating to the runtime statistics, the ISRs are dynamically re-assigned to the processors based on the runtime statistics in accordance with an optimization technique.