<p>The widespread growth in cancer cases worldwide necessitates an effective method for treating patients. This study focused on enhancing the efficacy of polyvinylidene difluoride-CoFe₂O₄ (PVDF-CFO) scaffolds for use in magnetic hyperthermia treatment (MHT) by enhancing fiber alignment. The Herman’s orientation factor (<i>f</i>), which represents the alignment degree of fibers, was calculated. Values of <i>f</i> = 0.4, 0.07, 0.1, and 0.2 were obtained for the prepared scaffolds at rotation speeds of 0, 1800, 3600, and 6000 rpm, respectively. The effect of the <i>f</i> factor on the microstructure, dielectric, piezoelectric, and magnetic properties of the scaffolds was evaluated. The average fiber diameter and open surface porosity of the scaffolds decreased with increasing <i>f</i> factor. With the incorporation of CFO and the enhancement of the alignment degree of fibers, the polymer β fraction was significantly increased, and a maximum of 97% β fraction was achieved. The dielectric, saturation magnetization, and piezoelectric sensitivity of the scaffolds increased with the <i>f</i> factor, with maximum values of 8.4 ± 0.5, 0.087 emg.g^–1, and 8.8 ± 0.4 V.N^–1, respectively. Heat generation was enhanced with increasing <i>f</i> factor. The maximum specific absorption rate (SAR) was 5.01 W.g^–1 and intrinsic loss power (ILP) values of 1.06 nHm²kg^–1 were obtained using a PVDF-CFO scaffold prepared with <i>f</i> = 0.2. The effectiveness of CFO incorporation on cancerous cell death (MCF7) was 7.6% over 48 h. The findings suggest that optimizing fiber orientation could be a key factor in improving the scaffolds' performance for thermal therapies for MHT applications.</p><p></p>