Soil- and seed-targeted delivery of nanomedicines for battling the pre-metastasis in the early stage of metastases. Besides targeting the seeds (DTCs) through optimized immuno-mediated recognition (Table 2), nanomedicines can be engineered to simultaneously target and destroy the soil (the pre-metastatic niche, PMN) by various routes including the repolarization of TAMs, the immunomodulation of stromal cells, the inhibition of MMPs, anti-angiogenesis and anti-lymphangiogenesis, where the synergistic therapy via the co-delivery of multi-drugs is applicable.