Postbiotics, considered the functional successors of live probiotics, retain most of probiotics’ structural and/or bioactive properties, and are key mediators of probiotic–environment interactions. Beyond influencing tumor proliferation, metastasis, and immune regulation, postbiotics can enhance the effectiveness of current anti-cancer treatments. Postbiotic-based cancer therapy represents an advanced evolution of bacterial treatment with improved safety and treatment potential. However, the field is limited by postbiotics’ imprecise definition and lack of standardized manufacturing methods, which together hinder their clinical application. Here, we establish a systematic classification of postbiotics based on their formation processes, focusing on the complex mechanisms underlying their activity in anti-tumor therapy, their therapeutic promise, and their current clinical use and challenges. Our aim is to guide future research, translation, and industrial development.