Scientific research is mainly based upon observation and experiment, and accordingly, the purpose of theoretical study is to provide the conceptual framework for the prediction and explanation of observation. Consequently, the combination of experimental and theoretical studies could potentially bring about the versatility and advancement in research. In this regard, this concept was applied toward the research theme of bio-oil upgrading. Bio-oil is a complex mixture of oxygenates, and hence, the study of an efficient catalyst requires the use of model oxygenate compounds such as phenolic and furanic derivatives. In this contribution, examples of the combined experimental and theoretical approaches will be given for the understanding toward the observation and fundamental studies of those model compounds on different classes of catalysts including zeolites, metals and carbon nanotube-metal oxide catalysts. The scope of these studies cover in several aspects ranging from physical to electronic phenomenon, such as hydrogen transfer ability of hydrocarbons which have an effect on product distribution and catalyst stability, possible reaction paths of anisole conversion on zeolites, alkylation of different aromatics on zeolites, metal-support interaction of nanohybrid catalysts, stability of intermediate species on metal catalysts, etc.