The present investigation reports the structural engineering of biodegradable star block polycaprolactone (PCL) to tailor-make aggregated micelles and unimolecular micelles to study their effect on drug delivery aspects in cancer cell lines. Fully PCL-based star block copolymers were designed by varying the arm numbers from two to eight while keeping the arm length constant throughout. Multifunctional initiators were exploited for stepwise solvent-free melt ring-opening polymerization of ε-caprolactone and γ-substituted caprolactone to construct star block copolymers having a PCL hydrophobic core and a carboxylic PCL hydrophilic shell, respectively. A higher arm number and a higher degree of branching in star polymers facilitated the formation of unimolecular micelles as opposed to the formation of conventional multimicellar aggregates in lower arm analogues. The dense core of the unimolecular micelles enabled them to load high amounts of the anticancer drug doxorubicin (DOX, ∼12–15%) compared to the aggregated micelles (∼3–4%). The star unimolecular micelle completely degraded leading to 90% release of the loaded drug upon treatment with the lysosomal esterase enzyme in vitro. The anticancer efficacies of these DOX-loaded unimolecular micelles were tested in a breast cancer cell line (MCF-7), and their IC50 values were found to be much lower compared to those of aggregated micelles. Time-dependent cellular uptake studies by confocal microscopy revealed that unimolecular micelles were readily taken up by the cells, and enhancement of the drug concentration was observed at the intracellular level up to 36 h. The present work opens new synthetic strategies for building a next-generation biodegradable unimolecular micellar nanoplatform for drug delivery in cancer research.