The large number of emerging contaminants is challenging scientist and also to governmental agencies due to the lack of knowledge about their environmental fate, behavior and potential toxic effects in short or medium/long terms. Pharmaceuticals, personal care products (PCPs), pesticides, herbicides or endocrine disrupting compounds have been contaminating environmental waters since long time. The potential risks that these contaminants may have in the ecosystems and on the public health are calling for more rapid, reliable and efficient technologies able to ensure food and environmental safety. At the same time, the so-called “omic” technologies are being used to study how chemicals in our environment may affect aquatic, terrestrial organisms and public health allowing to predict with more accuracy adverse responses to these chemicals. Mass spectrometry has been crucial for the development of this knowledge, but antibodies are also contributing to this fact. Thus, antibodies have fascinating features due to the possibility to be designed to bind almost any type of substance. Mass spectrometry immunoassay (MSIA) has found a broad application in bioanalysis and on proteomics. On top of this, there is the new knowledge on the unique properties of nanostructured materials with new optical and/or electrical properties. Improved transduction schemes with enhanced analytical features and multiplexed capabilities can be developed thanks to the novel micro/nano fabrication. All this knowledge allow envisaging a new generation enhanced high performance immunochemical analytical approaches that offer interesting alternatives to ensure safety of the population to the risks derived from all sources of contamination and emerging pollutants.