Eutrophication and global climate change gather advantageous conditions for cyanobacteria proliferation leading to bloom formation and cyanotoxin production. In the Azores, eutrophication is a major concern, mainly in lakes where fertilizers and organic matter discharges have increased nutrient concentration. In this study, we focused on understanding the influence of environmental factors and lake characteristics on (i) cyanobacteria diversity and biomass and (ii) the presence of toxic strains and microcystin, saxitoxin, anatoxin-a, and cylindrospermopsin cyanotoxin-producing genes. Fifteen lakes from the Azores Archipelago were sampled seasonally, environmental variables were recorded in situ, cyanobacteria were analyzed with microscopic techniques, and cyanotoxin-producing genes were targeted through conventional PCR. Statistical analysis (DistLM) showed that lake typology-associated variables (lake’s depth, area, and altitude) were the most explanatory variables of cyanobacteria biomass and cyanotoxin-producing genes presence, although trophic variables (chlorophyll a and total phosphorus) influence species distribution in each lake type. Our main results revealed higher cyanobacteria biomass/diversity, and higher toxicity risk in lakes located at lower altitudes, associated with deep anthropogenic pressures and eutrophication scenarios. These results emphasize the need for cyanobacteria blooms control measures, mainly by decreasing anthropogenic pressures surrounding these lakes, thus decreasing eutrophication. We also highlight the potential for microcystin, saxitoxin, and anatoxin-a production in these lakes, hence the necessity to implement continuous mitigation protocols to avoid environmental and public health toxicity events.