There are more than a billion people around the world diagnosed with diet-related diseases like diabetes and obesity, and the price tag for their care has ballooned to well over a trillion dollars per year. More effective and more affordable solutions are needed to prevent and manage these diseases, and personalized nutrition presents a high-potential mechanism to fulfill this need. However, there are as many opportunities as pitfalls in this space. In 2019, Campbell’s divested its $75 million investment into Habit. In the same year highly-funded startups uBiome and Arivale, backed by $110 million and $53 million, respectively, ceased operations entirely. Here we apply a four-part framework to assess these business failures in order to guide future decision-making and avoid expensive mistakes.