Cancer therapy continues to face major challenges, including drug resistance, toxicity, and tumor heterogeneity, which highlight the need for multitarget strategies. This review examines the molecular compatibility theory in integrative oncology, which combines traditional Chinese medicine (TCM) with systems biology to address these limitations. TCM formulas, such as Banxia Xiexin decoction and Qiqin Huchang formula, contain bioactive compounds (e.g., quercetin and berberine) that modulate interconnected pathways (phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase) and the tumor microenvironment, thereby promoting apoptosis, inhibiting angiogenesis, and regulating immune responses. The theory modernizes TCM’s “Jun-Chen-Zuo-Shi” principle by optimizing herb combinations through network pharmacology and omics technologies. For instance, Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (Huang Qi)–Curcuma phaeocaulis Val. (E Zhu) pairs co-target hypoxia-inducible factor 1-alpha to suppress metastasis, while artificial intelligence-driven models predict synergistic interactions such as quercetin–cyclin-dependent kinase 1 inhibition. Clinical studies have shown improved outcomes; for instance, modified Banxia Xiexin decoction reduces chemotherapy-induced toxicity in gastric cancer, and Xihuang pill enhances immunotherapy via signal transducer and activator of transcription 3–programmed death-ligand 1 modulation. Despite these advances, challenges remain in standardization and mechanistic validation. Future research should prioritize single-cell sequencing, organoid models, and international collaboration to refine personalized therapies and translate TCM into evidence-based oncology. By integrating empirical knowledge with modern science, molecular compatibility theory provides a robust framework for multitarget drug development and the advancement of integrative cancer therapies.