The macrolide (+)-discodermolide produced by the marine sponge Discodermia dissoluta shows promising antitumor, antimitotic, and immunosuppressive activity. However, the sustainable supply of any molecule requires much in situ and in vitro research to optimize and later obtain the molecule of interest. In this study, two culture systems—fixed and suspended—were evaluated at 15-m depth in two sites, Punta de Betín and Nenguange, in Santa Marta (Colombian Caribbean). Survival, growth, and production of (+)-discodermolide were recorded, with the suspended system resulting in better growth and survival, depending on the culture site. The influence of the different environmental factors on survival was also studied, and a negative correlation with temperature was observed. Salinity, solar radiation, organic matter, and water flow were not correlated. Finally, no significant differences in the production of (+)-discodermolide existed between the culture systems and study sites. Production ranged from 20 to 270 μg per gram of dry sponge.