Biological systems are intrinsically heterogeneous, from the level of molecular arrangements and interactions to whole tissue organization. To understand the complexity of these systems, it is fundamental to study their intricate structure and function in a spatially informed manner. Over the last decade, there has been a rapid advancement in the field of spatial omics, especially at the transcript level measuring gene expression, which has been instrumental in understanding how mRNA distribution and abundance define cell identity and function. This project aims to develop a highly multiplexed and modular methodology for integrated structural and multi-molecular characterization, as a means to visualize the spatial arrangement of the transcriptome with subcellular to tissue context. Given the importance of the compartmentalized organization of mRNAs (local transcriptome) in neurons, we apply a 242-gene panel to target neuron-specific transcripts in mouse brain tissue via Multiplexed Error Robust FISH (MERFISH). Importantly, we have adapted our protocols to work with thicker sections and gain 3D MERFISH spatial information. We also combine the transcriptional information with a morphological readout based on labeling the extracellular domain, which provides us with richer contextual information and allows us to locate mRNAs within distinct neuronal compartments at subcellular resolution. We envision that this technology will enable a more accurate characterization of the local transcriptome, to achieve a better understanding of how neurons respond to their functional demands in both health and disease.