High power consumption not only leads to short battery life for handheld devices, but also causes on-chip thermal and reliability problems in general. As power consumption is proportional to the square of supply voltage, reducing supply voltage can significantly reduce power consumption. Multi-supply voltage (MSV) has previously been introduced to provide finer-grain power and performance trade-off. In this work we propose a methodology on top of a set of algorithms to exploit non-trivial voltage island boundaries for optimal power versus design cost trade-off under performance requirement. Our algorithms are efficient, robust and error-bounded, and can be flexibly tuned to optimize for various design objectives (e.g., minimal power within a given number of voltage islands, or minimal fragmentation in voltage islands within a given power bound) depending on the design requirement. Our experiment on real industry designs shows a ten-fold improvement of our method over current logical-boundary based industry approach.