During the past decade, novel revolutionary frontiers have been opened at the immuno-inflammatory research fields. State-of-the-art technologies, including immunomics and systems biology, have shed a light on the complexity of the immune system, which had been underestimated before. It is now known that, to function properly, the immune system relies on multi-directional intercellular communications between cellular and humoral components of the innate and the adaptive immunity. Furthermore, communication between the immune system and the versatile and complex microbiota inhabiting the barrier surfaces of the human body is essential for the homeostatic regulation of immune-inflammatory responses. Importantly, altered immunological and (chronic) inflammation-related regulations play key roles in the pathogenesis of multiple cardiovascular and metabolic diseases, such as atherosclerosis and obesity, as well as in cancer initiation, development, and progression. These diseases, both the classical immuno-inflammatory as well as the immuno-inflammatory-related, are now considered the most prevalent human pathologies. In order to manage such immuno-inflammatory conditions, novel therapeutic strategies are required. Efforts have been made towards the generation of personalized pharmacological, biological, and (possibly) gene therapeutic solutions. These combined therapeutic protocols can only be successful if future research systematically uncovers the often redundant underlying genetic, transcriptomic, molecular, cellular and intercellular immune signalling pathways. It is also important to define those functional patterns whose genetic or acquired alterations could lead to the manifestation of the given pathology.