Cyanobacteria harmful algal blooms (CHABs) are a growing water quality problem in the upper San Francisco Estuary (California), also known as the Sacramento-San Joaquin Delta. We conducted cyanobacteria and cyanotoxin monitoring from 2020 to 2023, which spanned California's driest consecutive 3-year period and one of the wettest years on record (2023). To assess the impact of CHABs over this range of hydrologic conditions, we monitored invasive Asian Clams (Corbicula fluminea) for microcystin contamination and used molecular tools (qPCR and sequencing) to characterize cyanobacteria in the water column. We also used solid phase adsorption toxin tracking (SPATT) samplers to track microcystins (MCs) and other cyanotoxins in 2023. During the drought years, record breaking MCs, in excess of 1000 μg/L, were documented in water grab samples and Asian clams also accumulated higher MCs relative to the wet year. However, MCs were present in Asian clams during the entire study period. SPATT's confirmed MC presence during wet 2023 and sequencing results corroborated the integrative sampler findings. Yet, no MC was detected in water grab samples at our primary sampling sites during the drought year of 2022 or the wet year of 2023. This highlights the importance of using multiple sampling modalities to provide a more accurate assessment of MC contamination, especially in large estuaries where traditional discrete monitoring can easily miss episodic and transient CHAB events.