It is substituting the words how come for why can sometimes result in a sentence that doesn't make sense. The usage of both openers should always be appropriate within the context. In formal situations, why is almost always the correct word? It is also preferred for developing interrogative sentences. On the other hand, how come is used for informal or casual situations? How come is even uttered by children when they first learn a language at the dawn of their education.
How come may also indicate a question? It can either be accusatory or a gentle inquiry. It may be used to express disbelief within the context of its usage. For example, someone says, "I quit my job." And the accusatory response of doubt would be "how come." Another example is if someone says, "I don't feel good," the question would be, "how come?"