A method and system of improved reliability testing includes providing a first substrate and a second substrate, each substrate comprising only a first metallization layer; processing regions on a first substrate by combinatorially varying at least one of materials, unit processes, and process sequences; performing a first reliability test on the processed regions on the first substrate to generate first results; processing regions on a second substrate in a combinatorial manner by varying at least one of materials, unit processes, and process sequences based on the first results of the first reliability test; performing a second reliability test on the processed regions on the second substrate to generate second results; and determining whether the first substrate and the second substrate meet a predetermined quality threshold based on the second results.