This volume consists of a collection of 14 accepted submissions (including several invited feature articles) to the Special Issue of MDPI's journal Symmetry on the general subject area of integral transformations, operational calculus and their applications from many different parts around the world. The main objective of the Special Issue was to gather review, expository, and original research articles dealing with the state-of-the-art advances in integral transformations and operational calculus as well as their multidisciplinary applications, together with some relevance to the aspect of symmetry. Various families of fractional-order integrals and derivatives have been found to be remarkably important and fruitful, mainly due to their demonstrated applications in numerous diverse and widespread areas of mathematical, physical, chemical, engineering, and statistical sciences. Many of these fractional-order operators provide potentially useful tools for solving ordinary and partial differential equations, as well as integral, differintegral, and integro-differential equations; fractional-calculus analogues and extensions of each of these equations; and various other problems involving special functions of mathematical physics and applied mathematics, as well as their extensions and generalizations in one or more variables.