Organic semiconductors are an exciting class of materials that have potential to produce low-cost, printable, and flexible electronic devices. Moving to the next generation of organic semiconductors that will result in greater efficiency requires advancements in the areas of materials chemistry, molecular assembly, predictive modelling, and device optimization. Here, we focus on morphology and demonstrate how it is linked to each of these areas. Understanding the connections among chemistry, thin film microstructure, and charge transport remains a major challenge in the field. We examined materials systems relevant to organic solar cells, memory devices, and transistors, with a focus on synchrotron-based X-ray techniques. For a blend of a polymer and small molecule, applicable to solar cells, control of molecular orientation in the small molecule is especially important for non-fullerene based molecules that exhibit anisotropic charge transport. In ferroelectric-semiconductor polymer blends used in organic memory, improved control over phase separation length scales is achieved by altering the chemistry of the semiconducting polymer to tune polymer-polymer interactions. Complementary simulations can facilitate characterization of organic semiconductors. First-principles predictions of X-ray absorption spectroscopy are applied to semiconducting polymers, and prove critical for understanding complex experimental data related to molecular orientation and electronic structure in general. Overall, these studies provide insights into key factors that should be considered in the development of new organic semiconductors.