Synthetic approaches are becoming increasingly important in oncological therapeutics as they overcome the limitations of conventional therapies by providing precision, specificity, and personalized intervention. These approaches are fundamentally based on three pillars: synthetic biology, synthetic chemistry, and synthetic lethality. Synthetic biology applies engineering principles to design living cells with customized functions, such as engineered bacteria, oncolytic viruses, and illustrated by rationally designed oncolytic viruses, tumor-tropic engineered bacteria, and next-generation immune cell platforms, including CAR-T, CAR-NK, and modular synthetic gene circuits competent for context-dependent cancer cell recognition, immune evasion modulation, and controlled cytotoxic payload release. Synthetic chemistry contributes by rationally designing novel small molecules, therapeutic agents, and epigenetic modulators with optimized pharmacokinetics and pharmacodynamic profiles, which exhibit superior tissue penetration and reduced systemic toxicity. These engineered agents also modulate immune checkpoints such as PD-1/PD-L1 and reprogram the tumor microenvironment to enhance antitumor immunity. Synthetic lethality, on the other hand, exploits non-oncogene addiction by targeting a unique genetic vulnerability in cancer cells, as seen with PARP inhibitors that effectively target BRCA1/2-mutated cancers. The simultaneous disruption of two essential genes becomes lethal when combined. Together, these synthetic approaches offer powerful yet sophisticated tools at the molecular level, enabling the delivery of precision therapies characterized by fewer side effects and greater potential for personalized oncology.