Co-crystallization of active pharmaceutical ingredients (APIs) with pharmaceutically acceptable additives has emerged as an alternative to current drug delivery systems for hydrophobic drugs, due to their high drug loading efficiency. During this process, we herein report that tannic acid (TA) can be used as an amphiphilic stabilizer for the model drug, paclitaxel (PTX), that results in the shape and morphology variations of the synthesized microstructures, depending on the synthetic environment. We observed that rapid co-precipitation of PTX and TA via dialysis in water resulted in unprecedented urchin-like supramolecular microstructures with high porosity. On the other hand, slow co-precipitation for several hours under static conditions without dialysis exhibited bundles of straight TA-coated PTX fibers without any pores. This was plausibly due to the dynamic change of both the building block concentration and the solvent composition occurring during the transition of the kinetic product to the thermodynamic product. Interestingly, the synthesized urchin-like porous structure further rapidly transformed into a spherical shape through the interaction with serum proteins by remodeling of the non-covalent interactions, which contributed to the overall therapeutic efficacy tested in vitro. Our results provide knowledge on the self-assembly behavior of the hydrophobic drug and amphiphilic stabilizer under dynamic conditions, and contribute to the development of novel strategies in designing drug formulations.