En is a French preposition that commonly appears in phrases borrowed from French. In this case, en route is a French phrase that means, roughly, on the way (OED).
Other common French loan phrases involving en include:
en avant - forward. 1823 Ld. Byron Let.
22 Apr. (1980) X. 156 But never mind—‘En Avant!’ live while you can.
en banc - all or a quorum of judges.
1986 J. Batten Judges 220 Before the Second World War, the appeal courts would sit en banc for the most part.
en déshabillé - in undress.
1877 C. Reade Woman-hater I. vii. 172 Let me catch her en déshabille, with her porter on one side, and her lover on the other.
en l'air - in the air, figuratively meaning unsupported.
1964 W. B. Pemberton Battles of Boer War vi. 164 The extreme right of the Boers was practically en l'air and deserted.
en plein - in full; betting entirely on one side or number in roulette.
1966 C. Robertson Judas Spies i. 9 He had been sitting at a roulette table..playing the even chances mostly, occasionally trying his luck en plein.
en pointe - dancing on the toe in ballet.
1959 Times 1 Sept. 11/3 Miss Doris Lainë..did a wonderfully neat hop en pointe.
en poste - in an official (usually diplomatic) position.
1962 John o' London's 31 May 517/1 While he was en poste in Paris he gathered much of the material.
en suite - forming a suite, often of adjoining rooms.
2006 Peak District Life Spring 33/3 Crisp blue and white striped bed linen and curtains give a fresh feel to the guest bedroom and en-suite bathroom.
Outside of French borrowing, this preposition en is not a generative English word. For instance, en the countertop, en road, or en top of the world don't work, except as an awkward substitution for in or on.