Magnetic hyperthermia (MH) based on magnetic nanoparticles (MNPs) is a promising adjuvant therapy for cancer treatment. Particle clustering leading to complex magnetic interactions affects the heat generated by MNPs during MH. The heat efficiencies, theoretically predicted, are still poorly understood because of lack of the control of the fabrication of such clusters with defined geometries and thus their functionality. This study aims to correlate the heating efficiency under MH of individually coated iron oxide nanocubes (IONCs) vs. soft colloidal nanoclusters made of small groupings of nanocubes arranged in different geometries. The controlled clustering of alkyl stabilized IONCs is achieved here during the water transfer procedure by tuning the fraction of the amphiphilic copolymer, poly(styrene-co-maleic anhydride) cumene terminated, to the nanoparticle surface. It is found that increasing the polymer-to-nanoparticle surface ratio leads to the formation of increasingly large nanoclusters with defined geometries. When compared to the individual nanocubes, we show here that controlled grouping of nanoparticles—so-called “dimers” and “trimers” comprised of two and three nanocubes, respectively—increases 2 specific absorption rate (SAR) values, while conversely, forming centrosymmetric clusters having more than four nanocubes leads to lower SAR values. Magnetization measurements and Monte-Carlo based simulations support the observed SAR trend, and reveal the importance of the dipolar interaction effect and its dependence on the details of the particle arrangements within the different clusters. individual nanocubes, we show here that controlled grouping of nanoparticles—so-called “dimers” and “trimers” comprised of two and three nanocubes, respectively—increases