A solvent responsive dynamic nanoscale metal‐organic framework (NMOF) [Zn(1 a)(H₂O)₂] has been devised based on the self‐assembly of Zn^II and asymmetric bola‐amphiphilic oligo‐(p‐phenyleneethynylene) (OPE) dicarboxylate linker 1 a having dodecyl and triethyleneglycolmonomethylether (TEG, polar) side chains. In THF solvent, NMOF showed nanovesicular morphology (NMOF‐1) with surface decorated dodecyl chains. In water and methanol, NMOF exhibited inverse‐nanovesicle (NMOF‐2) and nanoscroll (NMOF‐3) morphology, respectively, with surface projected TEG chains. The pre‐formed NMOFs also unveiled reversible solvent responsive transformation of different morphologies. The flexible NMOF showed cyan emission and no cytotoxicity, allowing live cell imaging. Cisplatin (14.4 wt %) and doxorubicin (4.1 wt %) were encapsulated in NMOF‐1 by non‐covalent interactions and, in vitro and in vivo drug release was studied. The drug loaded NMOFs exhibited micromolar cytotoxicity.