Backdoor attacks involve inserting poisoned samples during training, resulting in a model containing a hidden backdoor that can trigger specific behaviors without impacting performance on normal samples. These attacks are challenging to detect, as the backdoored model appears normal until activated by the backdoor trigger, rendering them particularly stealthy. In this study, we devise a unified inference-stage detection framework to defend against backdoor attacks. We first rigorously formulate the inference-stage backdoor detection problem, encompassing various existing methods, and discuss several challenges and limitations. We then propose a framework with provable guarantees on the false positive rate or the probability of misclassifying a clean sample. Further, we derive the most powerful detection rule to maximize the detection power, namely the rate of accurately identifying a backdoor sample, given a false positive rate under classical learning scenarios. Based on the theoretically optimal detection rule, we suggest a practical and effective approach for real-world applications based on the latent representations of backdoored deep nets. We extensively evaluate our method on 14 different backdoor attacks using Computer Vision (CV) and Natural Language Processing (NLP) benchmark datasets. The experimental findings align with our theoretical results. We significantly surpass the state-of-the-art methods, e.g., up to 300\% improvement on the detection power as evaluated by AUCROC, over the state-of-the-art defense against advanced adaptive backdoor attacks.