Marine sponges are a rich source of highly diversified bioactive compounds. These medicinally valuable molecules represent extreme physiological and ecological functions in sponges, more presumably involving in the resistance to the feeding by other marine organisms like fish and fouling by barnacles, bacteria, fungi, etc. This feature of attaining resistance made sponges as successful poriferans that possess an impressive array of biological properties ranging from antimicrobial to anticancerous activities. The diversified bioactive principle of sponges might be due to their spacio-temporal distribution and although, the gateway for exploiting the sponges for isolating these distinct, potential molecules is open, suitable technical and methodological approaches are yet to be implemented in order to bring the sponges as successful pharmaceutical leads in the field of marine biotechnology. Despite of the identified difficulties of marine sponge research from past few decades, one should concentrate not only on the basic and applied technical/methodological considerations, but also on the novel strategies like in vitro sponge cell, fragment and whole sponge culture; sponge symbiont cell culture; in situ and ex situ sponge cultivation; and sponge bioreactors and metagenomic approaches, for the successful exploitation of marine sponges towards the novelty in sponge biotechnology. The present review narrates the pros and cons of the nowadays-marine sponge research by focusing on the suggestive ecobiotechnological approaches, based on the latest studies for feasible ecological exploitation and biotechnological application of sponges from the sea.