Aquaculture, the world’s fastest growing food sector, produces over half of all fish for human consumption. Aquaculture feeds include fishmeal and fish oil, extracted from wild-caught fish such as sardines, and poses ecological, food security, and economic drawbacks. Microalgae, yeasts, fungi, bacteria, and other alternative ingredients show promise as potential ingredients in aquafeeds that provide protein/amino acids, lipids, or omega-3 sources and sources of bioactive molecules. This review article discusses the issues that the literature often lacks data on, such as the recent development of using microorganisms, technological innovation, challenges, and opportunities to develop a low environmental footprint of aquaculture diet. The ingredients often require novel processing technology to improve digestibility and fish growth and reduce antinutritional factors. This is an important gap to fill because microalgae are the most frequently used organism in fish feed, particularly as a dietary supplement or mixed with other ingredients. The production, processing, and formulating steps can affect the nutritional qualities. Stepwise strategies are required to evaluate these ingredients for feed application, and in this article, I articulated the stepwise key approaches of evaluating nutritional and environmental response metrics to develop highly sustainable aquaculture feed using these microorganisms, which would guide a more judicious inclusion of these novel ingredients.