•Heterogeneous blood perfusion mapping in spatial coordinates, ωb(x,y,z) using medical imaging.•Modified Pennes bioheat equation.•High perfusion, moderate perfusion, low perfusion, no perfusion.•Spatially varying blood perfusion term. The Pennes bioheat equation is a widely used mathematical model for predicting temperature distribution in biological tissues. However, it assumes homogeneous blood perfusion throughout the tissue, which may not accurately represent the complex perfusion patterns observed in tumors. In this study, we propose modification to traditional Pennes bioheat equation that incorporates the effects of perfusion heterogeneity by introducing a spatially varying perfusion term, represented by a perfusion coefficient, ωb(x,y,z) to account for local variations in blood flow at each spatial location within the biological tissue. Therefore, heterogeneous blood perfusion at each tumor tissue voxel location relax the uniform blood perfusion assumption. By incorporating these modifications, the model allows for a more realistic representation of the heat exchange between the biological tissue and blood flow, by predicting the non-uniform temperature distribution particularly in tumors with irregular blood vessel growth and organization, thereby facilitating treatment planning and optimization of thermal therapies, and leading to more effective therapeutic outcomes. The spatially varying perfusion coefficient can be obtained through advanced imaging techniques such as dynamic contrast-enhanced MRI or Doppler ultrasound enabling the assessment of perfusion heterogeneity in biological tissues. In conclusion, the modified Pennes bioheat equation offers a valuable tool for understanding the intricate relationship between with heterogeneous blood perfusion and temperature distribution in biological tissues, providing important insights to the thermal response of tumors and guiding the development of improved therapeutic strategies in optimizing cancer treatments. Heterogeneous blood perfusion, ωb(x,y,z) source map of image-extracted PC3 tumor anatomy in axial plane (X-Y), sagittal plane (Y-Z), coronal plane (X-Z), three-dimensional view (X-Y-Z) is shown. Spatial coordinates are mapped with Eucledian distance approach. The color gradient shows the resulting perfusion at each tumor tissue location (red is high, blue is low). The UBF (uniform tumor blood flow), represents an easy-to-heat perfusion pattern with uniform perfusion demarcation at meshing coordinates, ABF (annular tumor blood flow), refers to hard-to-heat perfusion pattern with annular rings one inside another, RBF (randomized tumor blood flow) possess regions of no perfusion (NP) referred to as central dead-necrotic core (NC) region free from potential blood vessels, high perfusion (HP) at tumor peripheral region (PR), low perfusion (LP) and moderate perfusion (MP) at intermediate regions (IR). The color gradient shows the resulting perfusion at each tumor tissue location (red is high, blue is low). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Display omitted