Endophytes are barely untapped as vital sources in the medicine. They are microorganisms which mostly exist in plants. As they are exploited, it is accepted that endophytes can produce active metabolites that possess same function as their hosts such as taxol, podophyllotoxin, hypericin, and azadirachtin. These metabolites have been promising potential usefulness in safety and human health concerns. We are supposed to adopt measures to raise production for the low yield of metabolites. This paper summarizes the latest advances in various bioprocess optimization strategies. These techniques can overcome the limitations associated with rare pharmaceutical metabolite-producing endophytic fungi. These strategies include strain improvement, genome shuffling, medium optimization, fermentation conditions optimization, addition of specific factor, addition of solid sorbent, and co-culturing. It will enable endophytes to produce high and sustainable production of rare pharmaceutical metabolites.