Worldwide methane hydrate exploration activities have entered a new stage after the real extraction tests in Japan (2013, 2017) and China (2017). However, from the current technological development stage to the next commercial production stage, there still exist a wide gap: complex underground reservoir conditions and flow parameters. Therefore, the target of the current study is to investigate the effects of layer inclination and horizontal reservoir parameter inhomogeneities on the gas production. It is found that for 10° inclination of model, the equivalent permeability show 50% decrease to achieve the same production rate. The horizontally-set “inner column” and “outer column” (with changes in porosity from 0.20, 0.38, 0.50; and 0.3, 0.4, 0.5 for hydrate saturation) have different trends: for cases with horizontal porosity changes, the production rate difference happens in the mid-term (>300 d) observation; for cases with horizontal hydrate saturation changes, the production differs in each case from the production initiation. For real production trial, such inhomogeneity effects have to be considered in order to estimate the initial production and to maintain stable production in the long-term.