Infertility due to nonobstructive azoospermia is treatable with the use of testicular sperm extraction and IVF. The optimal approach for sperm retrieval is microdissection testicular sperm extraction (mTESE). This systematic review summarizes and evaluates the literature pertaining to patient optimization before mTESE, mTESE technique, and post-mTESE testicular tissue processing. Preoperative patient optimization has been assessed in terms of adjuvant hormone therapy and varicocele repair. Limited data are available for adjuvant medical therapy, and although also limited, data for varicocele repair support increased sperm retrieval, pregnancy, and return of sperm to the ejaculate. Post-mTESE tissue processing has few comparative studies; however, most studies support the combination of mechanical mincing and use of type 4 collagenase for tissue disintegration along with pentoxifylline to assist in identifying motile and viable spermatozoa for intracytoplasmic sperm injection.