The dissociation of natural gas hydrate is an endothermic reaction controlled by heat transfer, which is closely associated with the employed exploitation methods and well configurations. The main purpose of this study is to investigate the relationship between heat transfer and gas hydrate dissociation in a cuboid pressure vessel with different vertical well layouts (central well and side well) and production methods (pure depressurization (PD), depressurization combined with wellbore heating (DH), and huff and puff (HP)) through experimental and numerical simulations. The results show that the hydrate dissociation in the PD cases is promoted only by heat conduction from the surrounding environment. The heat transfer behaviors are basically the same when adopting depressurization with different wellbore locations. Addition of wellbore heating in the DH and HP cases will result in faster hydrate decomposition. However, heat conduction from the ambient will be impeded by wellbore heating. The cumulative heat transferred across the boundary will drop below 0 at a certain time, which would subsequently lead to a sharp rise of the heat loss. To reduce heat loss across the boundary, the heating section of the wellbore should be placed in the central area of the hydrate-bearing layer. In addition, it is found that intermittent heat injection with the HP method has the advantages of enhancing the heat convection effect and reducing the heat absorption of the hydrate deposit, which results in more favorable heat utilization efficiency and net energy gain.