The effect of well interference through fracture hits in shale reservoirs needs to be investigated because hydraulic fracturing is abundantly used in the development of unconventional oil and gas resources. Although numerous pressure tests have proven the existence of well interference, relatively few physical models exist to quantitatively simulate the pressure response of well interference. The objective of the present study is to develop a numerical, compositional model in combination with an embedded discrete fracture model (EDFM) to simulate well interference. Through non-neighboring connections, the EDFM can properly handle complex fracture geometries such as non-planar hydraulic fractures and a large amount of natural fractures. Based on public data for Eagle Ford shale oil, we build a reservoir model including up to three horizontal wells and five fluid pseudocomponents. The simulation results show that the connecting hydraulic fractures play a more important role than natural fractures in declining bottomhole pressure (BHP) of the shut-in well. Matrix permeability has a relatively minor impact on pressure drawdown and well productivity remains little affected due to the overall low permeability used. The BHP pressure decline profiles change from convex to concave when the conductivity of the connecting fractures increases. At early times, the BHP of the shut-in well decreases when the number of natural fractures increases. At later times, the natural fracture density has a lesser impact on the pressure response and no clear trend. The opening order of neighboring wells affects the well interference intensity between the target shut-in well with the surrounding wells. After a systematic investigation of pressure drawdown in the reservoir we formulate practical conclusions for improved production performance.