A method and system for selection of a primer set for a set of target sequences includes: identifying candidate fragments upon performance of a comparison operation with the set of target sequences; identifying a forward subset of unique forward candidates and a reverse subset of unique reverse candidates; reducing the forward subset and the reverse subset based on a filtering operation; performing an in silico search operation with the reduced forward subset and the reduced reverse subset; generating a set of candidate degenerate primers based on the in silico search operation and a base mismatch criterion; generating a reduced set of candidate degenerate primers upon filtering the set of candidate degenerate primers according to the set of primer criteria; and selecting forward primer subsets that amplify the set of target sequences and identifying a reverse primer subset for each of the forward primer subsets with an in silico PCR operation.