In this paper, we analyze the well-posedness of the Cauchy–Dirichlet problem to an integro-differential equation on a multidimensional domain Ω⊂Rn in the unknown u=u(x,t), Dtν0(ϱ0u)−Dtν1(ϱ1u)−L1u−∫0tK(t−s)L2u(x,s)ds=f(x,t)+g(u),0<ν1<ν0<1, where Dtνi are the Caputo fractional derivatives, ϱi=ϱi(x,t) with ϱ0≥μ0>0, and Li are uniform elliptic operators with time-dependent smooth coefficients. The principal feature of this equation is related to the integro-differential operator Dtν0(ϱ0u)−Dtν1(ϱ1u), which (under certain assumption on the coefficients) can be rewritten in the form of a generalized fractional derivative with a non-positive kernel. A particular case of this equation describes oxygen delivery through capillaries to tissue. First, under proper requirements on the given data in the linear model and certain relations between ν0 and ν1, we derive a priori estimates of a solution in Sobolev–Slobodeckii spaces that gives rise to providing the Hölder regularity of the solution. Exploiting these estimates and constructing appropriate approximate solutions, we prove the global strong solvability to the corresponding linear initial-boundary value problem. Finally, obtaining a priori estimates in the fractional Hölder classes and assuming additional conditions on the coefficients ϱ0 and ϱ1 and the nonlinearity g(u), the global one-valued classical solvability to the nonlinear model is claimed with the continuation argument method.