Obesity is a complex disorder resulting from the interplay of genetic, environmental, behavioral factors and life style and has a significant impact on the public health. The complexity of the disorder entails multidisciplinary research efforts involving various research disciplines to enhance the understanding of the molecular mechanisms implicated in the development of the disease. The disruption of the balance between energy intake and energy expenditure which leads to obesity involves the action of many contributing factors and many molecular compounds, making high-dimensional profiling very attractive. Nonetheless, despite definite advances in omics research over the last decade, many challenges remain, including combining data from the heterogeneous sources, development of data mining tools, and integrative analysis methodologies to fully exploit various hypotheses. This review presents a brief overview of ongoing research, summarizes current methodologies, techniques, and challenges in omics approaches to obesity research, and identifies areas of further research.