Gold NanoParticle (GNP) dose-enhanced radiation Therapy (GNPT) is a proposed radiotherapy approach which aims to improve dose localization. In complement to experimental techniques, Monte Carlo (MC) radiation transport simulations are used for GNPT dosimetry. Simulations on a tumour scale require complex geometry models that are reliable and efficient, two traits often in contention. This work introduces a general MC framework, the Heterogeneous MultiScale (HetMS) model, towards efficient and accurate GNPT simulation. The HetMS model combines distinct geometries of varying detail on different length scales into one simulation. The HetMS framework is implemented in the fast MC code EGSnrc. EGSnrc, with custom applications and geometries, is cross-validated with PENELOPE and Geant4-DNA MC codes and is tested for self-consistency, passing the electron Fano cavity test. Simulations of microscopic scoring cavities containing GNPs across a cm-scale phantom were constructed using the HetMS method, enabling fast MC calculations of tissue dose on a tumour scale. Dose Enhancement Factors (DEFs), ratio of dose to tissue with GNPs over dose to tissue without, were determined at various tumour positions for many different GNPT scenarios. A cell model, with nucleus and cytoplasm as two concentric spheres, containing GNPs is simulated. Less realistic but efficient modelling approaches of gold in the cell (e.g., a contiguous gold volume) are insufficient for realistic DEF calculations. Cell DEFs are sensitive to the distribution of GNPs within the cell, with highest DEFs for nucleus and cytoplasm when GNPs are distributed over nuclear surface. By investigating variable cell/nucleus size and fluctuations in gold to a target cell and 12 neighbouring cells, expected variation in cell DEF is determined. The above work is combined to create more detailed GNPT simulations. Cell DEFs are calculated at many positions within a tumour-sized volume, which, combined with the DEF variations computed previously provide a range of expected cell DEF at each position within the tumour. These simulations provide many useful metrics towards GNPT; e.g., the lesser DEFs expected for a cluster of cells, the depth at which the primary fluence attenuation from gold drops DEF below unity, and the feasibility of different GNP configurations.