The 4th International Conference on Mathematical Modelling, Applied Analysis and Computation-2021 (A Virtual Conference) was a specialized conference on mathematical modelling and its applications. The conference was dedicated to Prof. George A. Anastassiou, Department of Mathematical Sciences, University of Memphis, USA, who turned sixty-nine in November 2021. The scope of ICMMAAC-2021 conference covered theoretic and applied aspects of various types of mathematical modelling (Differential equations, Fractional differential equations, Distribution functions, Fuzzy mathematical models, etc.) for systems of dynamic nature (Deterministic, Stochastic, Continuous, Discrete or Hybrid with respect to time, etc.), applied analysis, and the usage of analytical and numerical techniques in handling modern problems of science, engineering, and finance. It aimed, in particular, at fostering cooperation among practitioners and theoreticians in this field.