1) It ignores the processes involved in burning fats, sugars, and proteins, which can heavily impact where your body prioritizes getting its energy (or storing it).
2) It ignores other health impacts of 'calories' such as blood glucose levels, which absolutely will depend on what it is you're eating and not just the calorie count. Sugars, fats, and carbs are also processed in different parts of your body - so you might be following a "calories in calories out" and giving yourself non-alcoholic fatty liver disease.
3) It conflates calories, as measured via completely artificial process, with human digestion.