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We describe the relative $K_0$-groups of orders in finite dimensional separable algebras over the fraction fields of Dedekind domains of characteristic zero in terms of the theory of reduced determinant functors introduced in [20]. We then use this approach to formulate, for each odd prime $p$, a main conjecture of non-commutative $p$-adic Iwasawa theory for $\mathbb{G}_m$ over arbitrary number fields. This conjecture predicts a precise relation between a canonical Rubin-Stark non-commutative Euler system that we define and the compactly supported $p$-adic cohomology of $\mathbb{Z}_p$ and simultaneously extends both the higher rank (commutative) main conjecture for $\mathbb{G}_m$ studied by Kurihara and the present authors and the formalism of main conjectures in non-commutative Iwasawa theory due to Ritter and Weiss and to Coates, Fukaya, Kato, Sujatha and Venjakob. Our approach also suggests a precise conjectural `higher derivative formula' for the Rubin-Stark non-commutative Euler system that extends the classical Gross-Stark Conjecture to the setting of Galois extensions of arbitrary number fields. We present strong evidence in support of both of these conjectures in the setting of arbitrary Galois CM extensions of totally real fields. In addition, in the general case, we show that the conjectures can be combined to establish a new strategy for obtaining evidence in support of the equivariant Tamagawa Number Conjecture for $\mathbb{G}_m$ over arbitrary Galois extensions.