RNA modifications represent a crucial class of post-transcriptional chemical alterations that profoundly regulate RNA stability and translational efficiency, thereby directly influencing cellular protein expression profiles. These diverse chemical marks are ubiquitously involved in and exert fine-tuned control over fundamental biological processes, including cell proliferation, differentiation, programmed cell death (apoptosis), and invasive metastatic potential. A pivotal advancement in this field has been the recognition that distinct types of RNA modifications do not function in isolation. Instead, they engage in intricate, dynamic interplay through multifaceted mechanisms such as synergistic enhancement, negative regulation, competitive occupancy, and functional crosstalk. Collectively, these interactions weave a sophisticated tapestry known as the "RNA modification interactome" or "RNA modification interaction network." The establishment and functional operation of this complex interactome rest fundamentally upon a multi-layered regulatory architecture formed by RNA-modifying enzymes. These catalytic enzymes, often termed "writers," "erasers," and sometimes "readers" in the context of their roles, exhibit hierarchical relationships within signaling cascades, acting in upstream-downstream regulatory sequences. Furthermore, they frequently converge at critical nodal points within parallel signaling pathways. Integration of their activities occurs through mechanisms such as the sharing of common regulatory factors or the assembly into functional multi-enzyme complexes. It is precisely this elaborate enzymatic network that directly orchestrates and profoundly shapes the interdependent relationships observed between different RNA modifications. This comprehensive review systematically delineates the molecular underpinnings of both direct and indirect interactions occurring between various RNA modifications. Building upon this foundational understanding of the interactome, the discussion progresses to introduce novel, innovative quantitative assessment frameworks and predictive disease models specifically engineered to leverage these intricate interaction patterns. Significantly, research conducted across diverse disease contexts has successfully identified downstream core signaling axes that are demonstrably driven by specific constellations of interacting RNA modifications. These discoveries extend beyond merely deepening our comprehension of the role RNA modification interplay plays in disease initiation and progression. They powerfully underscore the immense translational potential inherent in exploiting this knowledge for clinical applications. This potential manifests most concretely in the identification of novel diagnostic biomarkers derived from modification interaction signatures and the rational development of innovative therapeutic targets aimed at disrupting pathogenic modification networks. The synthesis of these findings provides an essential conceptual framework for comprehensively elucidating the multidimensional and dynamic regulatory functions orchestrated by RNA modifications within the cellular milieu. In summary, the emergent phenomenon of RNA modification crosstalk not only unveils the astonishing complexity inherent to the post-transcriptional regulatory landscape but also opens fundamentally new avenues of investigation. It provides critical insights and novel experimental paradigms for addressing the central mechanistic question of how RNA-modifying enzymes achieve exquisite substrate specificity—determining precisely which nucleotides within specific RNA molecules, often at defined developmental or pathological stages, become targets for selective chemical modification. Understanding these selectivity codes, heavily influenced by the modification interactome itself, is paramount for deciphering the full biological and pathological significance of the epitranscriptome.