The paper introduces DECOMP OPT, a novel structure-based molecular optimization method that combines a controllable and decomposed diffusion model to generate ligands with desired properties. The method addresses the limitations of existing 3D generative models in drug design by learning to generate ligands given target binding sites, while also optimizing these ligands to achieve specific properties such as high binding affinity and synthesizability. DECOMP OPT offers a unified framework for both de novo design and controllable generation, allowing for fine-grained control over substructures like arms and scaffolds. The method is evaluated on the CrossDocked2020 dataset, demonstrating superior performance in generating ligands with improved properties compared to strong de novo baselines and showing promising results in controllable generation tasks such as R-group design and scaffold hopping. The paper also includes ablation studies and comparisons with other methods, highlighting the effectiveness and advantages of DECOMP OPT in drug discovery.The paper introduces DECOMP OPT, a novel structure-based molecular optimization method that combines a controllable and decomposed diffusion model to generate ligands with desired properties. The method addresses the limitations of existing 3D generative models in drug design by learning to generate ligands given target binding sites, while also optimizing these ligands to achieve specific properties such as high binding affinity and synthesizability. DECOMP OPT offers a unified framework for both de novo design and controllable generation, allowing for fine-grained control over substructures like arms and scaffolds. The method is evaluated on the CrossDocked2020 dataset, demonstrating superior performance in generating ligands with improved properties compared to strong de novo baselines and showing promising results in controllable generation tasks such as R-group design and scaffold hopping. The paper also includes ablation studies and comparisons with other methods, highlighting the effectiveness and advantages of DECOMP OPT in drug discovery.