The world of microorganisms comprises a vast diversity of live organisms, each with its individual set of genes, cellular components and metabolic reactions that interact within the cell and communicate with the environment in many different ways. There is a strong imperative to gain a broader view of the wired and interconnected cellular and environmental processes as a whole via the systems microbiology approach in order to understand and predict ecosystem functioning. On the other hand, currently we experience a rise of metagenomics as an emerging tool to study communities of uncultured microorganisms. In this review, we conducted a survey of important methodologies in metagenomics and describe systems microbiology-like approaches for gaining a mechanistic understanding of complex microbial systems to interrogate compositional, evolutionary and metabolic properties. The review also discusses how metagenomics can be used as a holistic indicator for ecosystem response in terms of matter, nutrient and energy sources and functional networking.