Multi-modality profiling of single cells represents one of the latest technological advancements in molecular biology. Among various single-cell multi-modality strategies, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) allows simultaneous quantification of two distinct species: RNA and surface marker proteins (ADT). Here, we introduce CiteFuse, a streamlined package consisting of a suite of tools for the pre-processing, modality integration, clustering, ADT evaluation, RNA-ADT network construction, differential expression analysis, and interactive web-based visualization of CITE-seq data. We show the integrative capacity of CiteFuse to fuse the two data types and its relative advantage against data generated from single modality profiling. Furthermore, we illustrate the pre-processing steps in CiteFuse and in particular a novel doublet detection method based on a combined index of cell hashing and transcriptome data. Collectively, we demonstrate the utility and effectiveness of CiteFuse for the integrative analysis of transcriptome and epitope profiles from CITE-seq data.